Quercitrin improves cardiac remodeling following myocardial infarction by regulating macrophage polarization and metabolic reprogramming.

The death and disability caused by myocardial infarction is a health problem that needs to be addressed worldwide, and poor cardiac repair and fibrosis after myocardial infarction seriously affect patient recovery. Postmyocardial infarction repair by M2 macrophages is of great significance for ventricular remodeling. Quercitrin (Que) is a common flavonoid in fruits and vegetables that has antioxidant, anti-inflammatory, antitumor and other effects, but whether it has a role in the treatment of myocardial infarction is unclear. In this study, we constructed a mouse myocardial infarction model and administered Que. We found through cardiac ultrasound that Que administration improved cardiac ejection fraction and reduced ventricular remodeling. Staining of heart sections and detection of fibrosis marker protein levels revealed that Que administration slowed fibrosis after myocardial infarction. Flow cytometry showed that the proportion of M2 macrophages in the mouse heart was increased and that the expression levels of M2 macrophage markers were increased in the Que-treated group. Finally, we identified by metabolomics that Que reduces glycolysis, increases aerobic phosphorylation, and alters arginine metabolic pathways, polarizing macrophages toward the M2 phenotype. Our research lays the foundation for the future application of Que in myocardial infarction and other cardiovascular diseases.

Super-resolution terahertz imaging based on a meta-waveguide.

A terahertz metamaterial waveguide (meta-waveguide) and a meta-waveguide-based lens-free imaging system are presented. The meta-waveguide not only inherits the low-loss transmission performance of a waveguide but also breaks through the diffraction limit under the action of the metamaterial, achieving subwavelength focusing. The focusing distance is far greater than the Rayleigh length, thus enabling far-field scanning imaging. For verification, a metal ring-based meta-waveguide was fabricated by 3D printing and metal cladding technology. Then, a transmission scanning imaging system working at 0.1 THz was built. High quality terahertz images with a resolution of 1/3 of the wavelength were obtained by placing the imaging targets at the focus and performing two-dimensional scanning. The focusing and transmission of terahertz wave in the meta-waveguide were simulated and analyzed.

Nitrogen and nitrous oxides emission characteristics of anoxic/oxic wastewater treatment process under different oxygen regulation strategies.

Nitrous oxide (N2O) and nitrogen oxides (NOx) (i.e., nitric oxide (NO) and nitrogen dioxide (NO2)), which could be produced in wastewater treatment process and result in greenhouse effect and atmospheric pollution, respectively, have been studied limitedly in their emission characteristics and transformation mechanisms. In this study, intelligent oxygen regulation was applied in anoxic/oxic wastewater treatment process (I-A/O), and its effects on regulating NOx and N2O transformations were extensively explored by comparing it with conventional A/O process (C-A/O). Results showed that the average emission amounts of N2O and NOx in I-A/O were 7.45 ± 0.66 mg and 1.88 ± 0.10 mg, respectively. Satisfactory reduction of N2O by 29.28 %-45.08 % was achieved in I-A/O compared to that of C-A/O, but together with increased NOx emission by 83.19 %-120.57 %. Pearson correlation and transcriptional analysis suggested that NO2--N reduction in the anoxic phase dominated N2O production, while no significant N2O production in the oxic phase was found. Hence, the reduced N2O production in I-A/O was mainly attributed to its efficient denitrification process. On the other hand, both the anoxic and oxic phases played important roles in NO production. More importantly, sufficient oxygen in I-A/O promoted the ammonia oxidation process, resulting in higher NO emission in I-A/O in the oxic phase. The imbalance in NO and N2O emissions was then amplified by the NOR enzyme, which mediates the conversion of NO to N2O in both the anoxic and oxic phases. Besides, carbon emission reduction by 31.32 %-36.50 % was obtained in I-A/O due to aeration consumption savings and greenhouse gas emissions reduction compared to C-A/O. Overall, intelligent oxygen regulation optimized the nitrogen transformation and achieved carbon emission reduction in A/O process, but special attention should be paid to the associated risk caused by increased NO emissions.

Single-Cell RNA-Seq Analysis Reveals Macrophages Are Involved in the Pathogenesis of Human Sporadic Acute Type A Aortic Dissection.

Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.

Plasma Exosome miRNAs Profile in Patients With ST-Segment Elevation Myocardial Infarction.

Background: Circulating microRNAs (miRNAs) have been found to have different expressions in different phases of acute myocardial infarction. The profiles of plasma exosome miRNAs in patients with ST-segment elevation myocardial infarction (STEMI) at 3-6 months postinfarction are unknown. Objective: The aim of this study was to assess the profiles of plasma exosome miRNAs in patients with STEMI in comparison with healthy volunteers and to select specific exosome miRNAs related to pathophysiological changes post-STEMI. Methods: Plasma and echocardiography parameters were collected from 30 patients 3-6 months after STEMI and 30 healthy volunteers. Plasma exosome miRNAs were assessed by using high-throughput sequence (Illumina HiSeq 2500) and profile of the plasma exosome miRNAs was established in 10 patients and 6 healthy volunteers. The specific exosome miRNAs related to heart diseases were selected according to the TargetScan database. The specificity of the selected exosome miRNAs was evaluated in additional 20 post-STEMI patients and 24 healthy volunteers by using quantitative PCR (qPCR). Left ventricular remodeling (LVR) was defined using the European Association of Cardiovascular Imaging criteria according to echocardiography examination. Correlations between expression of the specific miRNAs and echocardiography parameters of LVR were assessed using the Spearman correlation analysis. Results: Twenty eight upregulated miRNAs and 49 downregulated miRNAs were found in patients 3-6 months after STEMI (p < 0.01) in comparison with the healthy volunteers. The two least expressed and heart-related exosome miRNAs were hsa-miR-181a-3p (0.64-fold, p < 0.01) and hsa-miR-874-3p (0.50-fold, p < 0.01), which were further confirmed by using qPCR and demonstrated significant specificity in another 20 patients with post-STEMI comparing to 24 healthy volunteers [area under the curve (AUC) = 0.68, p < 0.05; AUC = 0.74, p < 0.05]. The expression of hsa-miR-181a-3p was downregulated in patients with LV adverse remodeling in comparison with patients without LV adverse remodeling and healthy volunteers. Conclusion: Circulating exosome miR-874-3p and miR-181a-3p were downregulated in patients with STEMI postinfarction. Exosome hsa-miR-181a-3p might play a potential role in the development of LVR in patients with post-STEMI.

Integrated metabolomic and gene expression analyses to study the effects of glycerol monolaurate on flesh quality in large yellow croaker (Larimichthys crocea).

To improve the quality of cultured large yellow croaker (Larimichthys crocea), this study was performed to study the impacts of glycerol monolaurate (GML) on the nutritional value, growth performance, muscle texture, and taste intensity of L. crocea. The results showed that GML as a feed additive significantly increased the crude lipid content and reduced the diameters of muscle fibers, which in turn markedly altered the flesh texture in terms of cohesiveness. Moreover, the taste indicators (umami and richness) and flavor-related amino acid (glutamic acid, glycine, and proline) contents of L. crocea muscle were significantly higher in the GML group. Metabolomic and gene expression analyses showed that GML supplementation could significantly improve amino acid biosynthesis and metabolism, promote protein and lipid synthesis, and activate myogenic-related signaling pathways of L. crocea. Consequently, adding an appropriate amount of GML to fish feed would be conducive to providing healthy, nutrient-rich and acceptably flavored aquatic-products.

Construction of the gene expression subgroups of patients with coronary artery disease through bioinformatics approach.

Coronary artery disease (CAD) is a heterogeneous disease that has placed a heavy burden on public health due to its considerable morbidity, mortality and high costs. Better understanding of the genetic drivers and gene expression clustering behind CAD will be helpful for the development of genetic diagnosis of CAD patients. The transcriptome of 352 CAD patients and 263 normal controls were obtained from the Gene Expression Omnibus (GEO) database. We performed a modified unsupervised machine learning algorithm to group CAD patients. The relationship between gene modules obtained through weighted gene co-expression network analysis (WGCNA) and clinical features was identified by the Pearson correlation analysis. The annotation of gene modules and subgroups was done by the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Three gene expression subgroups with the clustering score of greater than 0.75 were constructed. Subgroup I may experience coronary artery disease of an in-creased severity, while subgroup III is milder. Subgroup I was found to be closely related to the upregulation of the mitochondrial autophagy pathway, whereas the genes of subgroup II were shown to be related to the upregulation of the ribosome pathway. The high expression of APOE, NOS1 and NOS3 in the subgroup I suggested that the patients had more severe coronary artery disease. The construction of genetic subgroups of CAD patients has enabled clinicians to improve their understanding of CAD pathogenesis and provides potential tools for disease diagnosis, classification and assessment of prognosis.

Utility of NT-proBNP as an objective marker of postoperative heart failure after coronary artery bypass surgery: a prospective observational study.

BACKGROUND: Postoperative heart failure (PHF) is the main cause for mortality after cardiac surgery but unbiased evaluation of PHF is difficult. We investigated the utility of postoperative NT-proBNP as an objective marker of PHF after coronary artery bypass surgery (CABG). METHODS: Prospective study on 382 patients undergoing isolated CABG for acute coronary syndrome. NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A blinded Endpoints Committee used prespecified criteria for PHF. Use of circulatory support was scrutinized. RESULTS: After adjusting for confounders PHF was associated with 1.46 times higher NT-proBNP on POD1 (p = 0.002), 1.54 times higher on POD3 (p < 0.0001). In severe PHF, NT-proBNP was 2.18 times higher on POD1 (p = 0.001) and 1.81 times higher on POD3 (p = 0.019). Postoperative change of NT-proBNP was independently associated with PHF (OR 5.12, 95% CI 1.86-14.10, p = 0.002). The use of inotropes and ICU resources increased with incremental quartiles of postoperative NT-proBNP. CONCLUSIONS: Postoperative NT-proBNP can serve as an objective marker of the severity of postoperative myocardial dysfunction. Due to overlap in individuals, NT-proBNP is useful mainly for comparisons at cohort level. As such, it provides a tool for study purposes when an unbiased assessment of prevention or treatment of PHF is desirable. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00489827 https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=2&rank=1 .

The impact of glutamate infusion on postoperative NT-proBNP in patients undergoing coronary artery bypass surgery: a randomized study.

BACKGROUND: Glutamate, a key intermediate in myocardial metabolism, may enhance myocardial recovery after ischemia and possibly reduce the incidence and severity of postoperative heart failure in coronary artery bypass surgery (CABG). N-terminal pro-B-type natriuretic peptide (NT-proBNP) can be used to assess postoperative heart failure (PHF) after CABG. Our hypothesis was that glutamate enhances myocardial recovery in post-ischemic heart failure and, therefore, will be accompanied by a mitigated postoperative increase of NT-proBNP. METHODS: Substudy of the GLUTAmate for Metabolic Intervention in Coronary Surgery (GLUTAMICS) trial (ClinicalTrials.gov Identifier: NCT00489827) a prospective triple-center double-blind randomized clinical trial on 399 patients undergoing CABG with or without concomitant procedure for acute coronary syndrome at three Swedish Cardiac Surgery centres (Linköping, Örebro, and Karlskrona) from May 30, 2007 to November 12, 2009. Patients were randomly assigned to intravenous infusion of 0.125 M L-glutamic acid or saline (1.65 mL/kg of body weight per hour) intraoperatively and postoperatively. Plasma NT-proBNP was measured preoperatively, the first (POD1) and third postoperative morning (POD3). A Clinical Endpoints Committee, blinded to both intervention and NT-proBNP used prespecified criteria to diagnose PHF. The primary endpoints were the absolute levels of postoperative NT-proBNP and the difference between preoperative and postoperative levels of NT-proBNP. RESULTS: Overall no significant difference was detected in postoperative NT-proBNP levels between groups. However, in high-risk patients (upper quartile of EuroSCORE II ≥ 4.15; glutamate group n = 56; control group n = 45) glutamate was associated with significantly lower postoperative increase of NT-proBNP (POD3-Pre: 3900 [2995-6260] vs. 6745 [3455-12,687] ng•L-1, p = 0.012) and lower NT-proBNP POD3 (POD3: 4845 [3426-7423] vs. 8430 [5370-14,100] ng•L-1, p = 0.001). After adjusting for significant differences in preoperative demographics, NT-proBNP POD3 in the glutamate group was 0.62 times of that in the control group (p = 0.002). Patients in the glutamate group also had shorter ICU stay (21 [19-26] vs. 25 [22-46] h, p = 0.025) and less signs of myocardial injury (Troponin T POD3 (300 [170-500] vs. 560 [210-910] ng•L-1, p = 0.025). CONCLUSIONS: Post hoc analysis of postoperative NT-proBNP suggests that intravenous infusion of glutamate may prevent or mitigate myocardial dysfunction in high-risk patients undergoing CABG. Further studies are necessary to confirm these findings. Trial registration Swedish Medical Products Agency 151:2003/70403 (prospectively registered with amendment about this substudy filed March 17, 2007). ClinicalTrials.gov Identifier: NCT00489827 (retrospectively registered) https://clinicaltrials.gov/ct2/show/NCT00489827?term=glutamics&draw=1&rank=1.

NT-proBNP and postoperative heart failure in surgery for aortic stenosis.

Objective: Postoperative heart failure (PHF) after aortic valve replacement (AVR) for aortic stenosis (AS) may initially appear mild and transient but has serious long-term consequences. Methods to assess PHF are not well documented. We studied the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and PHF after AVR for AS. Methods: This is a prospective, observational, longitudinal study of 203 patients undergoing elective first-time AVR for AS. Plasma NT-proBNP was assessed at preoperative evaluation, the day before surgery, and the first (POD1) and third postoperative morning. A clinical endpoints committee, blinded to NT-proBNP results, used prespecified haemodynamic criteria to diagnose PHF. The mean follow-up was 8.6±1.1 years. Results: No patient with PHF (n=18) died within 30 days after surgery, but PHF was associated with poor long-term survival (HR 3.01, 95% CI 1.45 to 6.21, p=0.003). NT-proBNP was significantly higher in patients with PHF only on POD1 (6415 (3145-11 220) vs 2445 (1540-3855) ng/L, p<0.0001). NT-proBNP POD1 provided good discrimination of PHF (area under the curve=0.82, 95% CI 0.72 to 0.91, p<0.0001; best cut-off 5290 ng/L: sensitivity 63%, specificity 85%). NT-proBNP POD1 ≥5290 ng/L identified which patients with PHF carried a risk of poor long-term survival, and PHF with NT-proBNP POD1 ≥ 5290 ng/L emerged as a risk factor for long-term mortality in the multivariable Cox regression (HR 6.20, 95% CI 2.72 to 14.1, p<0.0001). Conclusions: The serious long-term consequences associated with PHF after AVR for AS were confirmed. NT-proBNP level on POD1 aids in the assessment of PHF and identifies patients at particular risk of poor long-term survival.

Impact of underlying heart disease per se on the utility of preoperative NT-proBNP in adult cardiac surgery.

OBJECTIVE: The primary aim was to investigate the role of underlying heart disease on preoperative NT-proBNP levels in patients admitted for adult cardiac surgery, after adjusting for the known confounders age, gender, obesity and renal function. The second aim was to investigate the predictive value of preoperative NT-proBNP with regard to severe postoperative heart failure (SPHF) and postoperative mortality. METHODS: A retrospective cohort study based on preoperative NT-proBNP measurements in an unselected cohort including all patients undergoing first time surgery for coronary artery disease (CAD; n = 2226), aortic stenosis (AS; n = 406) or mitral regurgitation (MR; n = 346) from April 2010 to August 2016 in the southeast region of Sweden (n = 2978). Concomitant procedures were not included, with the exception of Maze or tricuspid valve procedures. RESULTS: Preoperative NT-proBNP was 1.67 times (p<0.0001) and 1.41 times (p<0.0001) higher in patients with AS or MR respectively, than in patients with CAD after adjusting for confounders. NT-proBNP demonstrated significant discrimination with regard to SPHF in CAD (AUC = 0.79, 95%CI 0.73-0.85, p<0.0001), MR (AUC = 0.80, 95%CI 0.72-0.87, p<0.0001) and AS (AUC = 0.66, 95%CI 0.51-0.81, p = 0.047). In CAD patients NT-proBNP demonstrated significant discrimination with regard to postoperative 30-day or in-hospital mortality (AUC = 0.78; 95%CI 0.71-0.85, p<0.0001). The number of deaths was too few in the AS and MR group to permit analysis. Elevated NT-proBNP emerged as an independent risk factor for SPHF, and postoperative mortality in CAD. CONCLUSIONS: Patients with AS or MR have higher preoperative NT-proBNP than CAD patients even after adjusting for confounders. The predictive value of NT-proBNP with regard to SPHF was confirmed in CAD and MR patients but was less convincing in AS patients.

Prostaglandin E1 protects bone marrow-derived mesenchymal stem cells against serum deprivation-induced apoptosis.

Mesenchymal stem cells (MSCs) have become a recent focus of experimental and clinical research regarding myocardial regeneration. However, the therapeutic potential of these cells is limited by poor survival. Prostaglandin E1 (PGE1) is known to have anti­inflammatory and anti­apoptotic effects on the myocardium. The aim of the present study was to determine whether PGE1 could protect MSCs against serum deprivation (SD)­induced apoptosis. An SD model was used to induce apoptosis in MSCs in vitro. Apoptotic morphological changes were detected by Hoechst 33258 fluorescent nuclear staining; and Annexin V­fluorescein isothiocyanate/propidium iodide (PI) double staining and flow cytometry was used to quantify the rate of apoptosis. Western blot analysis was used to detect the expression levels of the apoptosis­associated proteins Bcl­2, Bax and caspase­3. The results of the present study demonstrated that SD induced apoptosis of MSCs, and that treatment with PGE1 attenuated the morphological changes characteristic of apoptosis. Annexin V/PI staining showed that the rate of apoptosis gradually increased with the duration of ischemia. Furthermore, treatment with PGE1 significantly reduced SD­induced apoptosis, decreased the protein expression levels of Bax and caspase­3, and increased the expression levels of Bcl­2. These data suggest that PGE1 is able to influence the survival of MSCs under certain conditions. These results may aid in improving the therapeutic efficacy of MSC transplantation used to treat chronic ischemic heart disease.

Multimodality treatment for cardiac angiosarcoma.

Primary cardiac angiosarcoma is a rare and highly malignant condition. Besides performing complete surgical excision, it remains controversial as to whether survival can be improved with additional treatment. We herein describe a 30-year-old man with a right atrial angiosarcoma. He underwent two operations for the resection of the primary lesion, and the patient's metastatic lesions involved an intestinal segment. With chemotherapy, radiotherapy, and molecular targeted therapy, he survived for 33 months. The literature describing adjuvant therapy for cardiac angiosarcoma, which is mostly case reports, is also reviewed. In conclusion, the limited evidence suggests that multimodality treatment for cardiac angiosarcoma is a beacon of hope to improve the survival of such patients.

Inhibition of apoptosis by knockdown of caspase-3 with siRNA in rat bone marrow mesenchymal stem cells.

Transplantation of bone marrow mesenchymal stem cells is a promising new strategy for the repair of infarcted cardiac tissue. However, the majority of transplanted bone marrow mesenchymal stem cells (BMSCs) die soon after transplantation, due in part to oxidative stress in the ischemic region. Oxidative stress is known to induce apoptosis through the activation of caspase-3. The aim of this study is to determine whether small interfering RNA targeting caspase-3 can inhibit the apoptosis of rat BMSCs in vitro. Caspase-3 siRNA expression vectors were prepared and transfected into rat BMSCs in the presence of liposomes. Western blot assay and real-time polymerase chain reaction (RT-PCR) were performed to detect caspase-3 expression. A retrovirus packaging system was employed to package 293FT cells producing caspase-3 siRNA virus, which were transfected into rat BMSCs. Those stably expressing caspase-3 siRNA were screened by Western blot assay and RT-PCR to determine caspase-3 expression levels. Stable transfection of caspase-3 siRNA significantly decreased caspase-3 protein (0.26 ± 0.001 vs. 0.42 ± 0.004, P < 0.05) and mRNA expression (0.19 ± 0.002 vs. 1, P < 0.05) in BMSCs compared to non-transfected BMSCs. Cells were incubated in H2O2 to induce apoptosis, which was detected by TUNEL staining, and BMSC morphology was not altered by either transient or stable transfection of caspase-3 siRNA. H2O2-induced apoptosis of BMSCs stably transfected with caspase-3 siRNA was dramatically reduced compared to that of normal BMSCs (11.0 ± 3.2 vs. 25.8 ± 4.2, P < 0.05). Caspase-3 knockdown BMSCs are thus more resistant to apoptosis than normal BMSCs, potentially increasing their survival rates under conditions that cause oxidative stress.