Terahertz s-SNOM Imaging of a Single Cell with Nanoscale Resolution.

Terahertz scattering scanning near-field optical microscopy is a robust spectral detection technique with a nanoscale resolution. However, there are still major challenges in investigating the heterogeneity of cell membrane components in individual cells. Here, we present a novel and comprehensive analytical approach for detecting and investigating heterogeneity in cell membrane components at the single-cell level. In comparison to the resolution of the topographical atomic force microscopy image, the spatial resolution of the terahertz near-field amplitude image is 3 times that of the former. This ultrafine resolution enables the compositional distribution in the cell membrane, such as the distribution of extracellular vesicles, to be finely characterized. Furthermore, via extraction of the near-field absorption images at specific frequencies, the visualization and compositional difference analysis of cell membrane components can be presented in detail. These findings have significant implications for the intuitive and visual analysis of cell development and disease evolutionary pathways.

Associations between serum electrolyte and short-term outcomes in patients with acute decompensated heart failure.

INTRODUCTION: There is a dearth of comprehensive studies on the association between serum electrolyte and adverse short-term prognosis of Chinese patients with acute decompensated heart failure (ADHF). PATIENTS AND METHODS: A total of 5166 patients with ADHF were divided into four serum electrolyte-related study populations (potassium (n = 5145), sodium (n = 5135), chloride (n = 4966), serum total calcium (STC) (n = 4143)) under corresponding exclusions. Different logistic regression models were utilized to gauge the association between these electrolytes or the number of electrolyte abnormalities and the risk of a composite of all-cause mortality or 30-day heart failure (HF) readmission. RESULTS: In multivariable adjusted analysis, patients with potassium below 3.5 mmol/L (odds ratios (ORs) 1.45; 95% confidence interval (CI):1.07-1.95), 4.01-4.50 mmol/L (OR: 1.29, CI: 1.02-1.62), 4.51-5.00 mmol/L (OR: 1.43, CI: 1.08-1.90) and above 5.00 mmol/L (OR: 1.74, CI: 1.21-2.51) had an increased risk of outcome when compared with potassium at 3.50-4.00 mmol/L. Sodium levels were inversely related to the risk of a composite outcome (<130 mmol/L: OR: 2.73 (95% CI, 1.81-4.12); 130-134 mmol/L: OR, 1.97 (CI, 1.45-2.68); 135-140 mmol/L: OR, 1.45 (CI, 1.17-1.81); p for trend < 0.001) in comparison with sodium at 141-145 mmol/L. Chloride < 95 mmol/L corresponded to a higher risk of a composite outcome with an OR of 1.65 (95% CI, 1.16-2.37) in contrast to chloride levels at 101-105 mmol/L. In addition, the adjusted ORs (95% CI) for a composite outcome comparing the STC < 2.00 and 2.00-2.24 vs. 2.25-2.58 mmol/L were 0.98 (0.69-1.43) and 1.13 (0.89-1.44), respectively. Besides that, the number of electrolyte abnormalities was positively related to the risk of a composite outcome (N = 1, OR 1.40, 95% CI: 1.13-1.73; N = 2, OR 2.51, 95% CI: 1.85-3.42; N = 3, OR 2.47, 95% CI: 1.45-4.19; p for trend < 0.001) in comparison with N = 0. CONCLUSIONS: A deviation of potassium levels from 3.50 to 4.00 mmol/L, lower sodium levels and hypochloremia were associated with poorer short-term prognosis of ADHF. Furthermore, the number of electrolyte abnormalities positively correlated with adverse short-term prognosis of patients with ADHF. Key MessagesADHF patients with baseline serum potassium at first half part of normal range (3.50-4.00 mmol/L) may herald the lowest risk of recent cardiovascular events.Serum sodium and chloride levels exhibit discrepancies in terms of risk of short-term adverse events of ADHF patients.The number of electrolyte abnormalities is a significant predictor of poor short-term prognosis in patients with ADHF. CLINICAL TRIAL REGISTRATION URL: http://www.chictr.org.cn/showproj.aspx?proj=23139. Unique identifier: ChiCTR-POC-17014020.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

Transcriptome sequencing and lncRNA-miRNA-mRNA network construction in cardiac fibrosis and heart failure.

Cardiac fibrosis (CF) and heart failure (HF) are common heart diseases, and severe CF can lead to HF. In this study, we tried to find their common potential molecular markers, which may help the diagnosis and treatment of CF and HF. RNA library construction and high-throughput sequencing were performed. The DESeq2 package in R was used to screen differentially expressed mRNAs (DEmRNAs), differentially expressed lncRNA (DElncRNAs) and differentially expressed miRNA (DEmiRNAs) between different samples. The common DEmRNAs, DElncRNAs and DEmiRNAs for the two diseases were obtained. The ConsensusPathDB (CPDB) was used to perform biological function enrichment for common DEmRNAs. Gene interaction network was constructed to screen out key genes. Subsequently, real-time polymerase chain reaction (RT-PCR) verification was performed. Lastly, GSE104150 and GSE21125 data sets were utilized for expression validation and diagnostic analysis. There were 1477 DEmRNAs, 502 DElncRNAs and 36 DEmiRNAs between CF and healthy control group. There were 607 DEmRNAs, 379DElncRNAs,s and 42 DEmiRNAs between HF and healthy control group. CH and FH shared 146 DEmRNAs, 80 DElncRNAs, and 6 DEmiRNAs. Hsa-miR-144-3p, CCNE2, C9orf72, MAP3K20-AS1, LEF1-AS1, AC243772.2, FLJ46284, and AC239798.2 were key molecules in lncRNA-miRNA-mRNA network. In addition, hsa-miR-144-3p and CCNE2 may be considered as potential diagnostic gene biomarkers in HF. In this study, the identification of common biomarkers of CF and HF may help prevent CF to HF transition as early as possible.

Exosomes derived from miR-129-5p modified bone marrow mesenchymal stem cells represses ventricular remolding of mice with myocardial infarction.

Myocardial infraction (MI) is a severe disease with great mortality. Mesenchymal stem cells-derived exosomes display protection against MI. MicroRNA-129-5p was reported to exert anti-inflammation activity by targeting high mobility group box 1 (HMGB1). In the present study, the effects of MSCs derived exosomes overexpressing miR-129-5p on MI were evaluated. Bone marrow mesenchymal stem cells (BMSCs) were transfected with miR-129-5p for exosomes isolation. Myocardial infraction mice model was established and administrated exosomes overexpressing miR-129-5p. The cardiac function, expression of HMGB1, inflammatory cytokines, apoptosis and fibrosis in heart tissues were measured. miR-129-5p inhibited HMGB1 expression in BMSCs. Myocardial infraction mice treated with exosomes overexpressing miR-129-5p had enhanced cardiac function and decreased expression of HMGB1 and production of inflammatory cytokines. Exosomes overexpressing miR-129-5p further prevented apoptosis and fibrosis. Exosome-mediated transfer of miR-129-5p suppressed inflammation in MI mice by targeting HMGB1.

Lipid goal attainment in post-acute coronary syndrome patients in China: Results from the 6-month real-world dyslipidemia international study II.

BACKGROUND: Dyslipidemia International Study II (DYSIS II)-China was conducted to determine the low-density lipoprotein cholesterol (LDL-C) goal (<1.8 mmol/L) attainment rate in patients with post-acute coronary syndrome (ACS). HYPOTHESIS: Compliance with treatment guideline recommendations improves the LDL-C goal attainment rate in post-ACS patients. METHODS: This multicenter prospective observational study conducted at 28 tertiary hospitals determined the LDL-C goal attainment rates at admission and 6-month follow-up in patients on lipid-lowering treatment (LLT) for ≥3 months and those not on LLT (LLT-naive or off LLT for ≥3 months) at admission. Predictors of goal attainment at 6 months were identified using multivariate logistic regression. RESULTS: The LDL-C goal attainment rate at admission in 1102/1103 enrolled patients was 17.1%; it was 41.2% among 752 patients with available lipid results at 6 months. The distance to goal was 0.7 mmol/L at 6 months. Statin monotherapy was the most prescribed LLT. Only 7.7% of patients were receiving statin + ezetimibe and 8.4% of patients were receiving an atorvastatin-equivalent dose of ≥40 mg/day at 6 months. Being male (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.6) and undergoing percutaneous coronary intervention during index hospitalization (OR 1.5, 95% CI 1.1 to 2.1) were the independent predictors for LDL-C goal attainment. CONCLUSIONS: This real-world DYSIS II study in China reports a low LDL-C goal attainment rate in post-ACS patients even after 6 months of LLT. Lack of intensification of statin therapy and underutilization of combinations suggest gaps between real-world treatment practices and guideline recommendations.

Uncovering Potential lncRNAs and mRNAs in the Progression From Acute Myocardial Infarction to Myocardial Fibrosis to Heart Failure.

Background: Morbidity and mortality of heart failure (HF) post-myocardial infarction (MI) remain elevated. The aim of this study was to find potential long non-coding RNAs (lncRNAs) and mRNAs in the progression from acute myocardial infarction (AMI) to myocardial fibrosis (MF) to HF. Methods: Firstly, blood samples from AMI, MF, and HF patients were used for RNA sequencing. Secondly, differentially expressed lncRNAs and mRNAs were obtained in MF vs. AMI and HF vs. MF, followed by functional analysis of shared differentially expressed mRNAs between two groups. Thirdly, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed in MF vs. AMI and HF vs. MF. Finally, expression validation and diagnostic capability analysis of selected lncRNAs and mRNAs were performed. Results: Several lncRNA-co-expressed/nearby targeted mRNA pairs including AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 were identified. Several signaling pathways including TNF and cytokine-cytokine receptor interaction, fructose and mannose metabolism and HIF-1, hematopoietic cell lineage and fluid shear stress, and atherosclerosis and estrogen were selected. IL1R2, IRAK3, LRG1, and PLAC4 had a potential diagnostic value for both AMI and HF. Conclusion: Identified AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 lncRNA-co-expressed/nearby targeted mRNA pairs may play crucial roles in the development of AMI, MF, and HF.

Terahertz Spectroscopy for Accurate Identification of Panax quinquefolium Basing on Nonconjugated 24(R)-Pseudoginsenoside F11.

Panax quinquefolium is a perennial herbaceous plant that contains many beneficial ginsenosides with diverse pharmacological effects. 24(R)-pseudoginsenoside F11 is specific to P. quinquefolium, a useful biomarker for distinguishing this species from other related plants. However, because of its nonconjugated property and the complexity of existing detection methods, this biomarker cannot be used as the identification standard. We herein present a stable 24(R)-pseudoginsenoside F11 fingerprint spectrum in the terahertz band, thereby proving that F11 can be detected and quantitatively analyzed via terahertz spectroscopy. We also analyzed the sample by high-performance liquid chromatography-triple quadrupole mass spectrometry. The difference between the normalized data for the two analytical methods was less than 5%. Furthermore, P. quinquefolium from different areas and other substances can be clearly distinguished based on these terahertz spectra with a standard principal component analysis. Our method is a fast, simple, and cost-effective approach for identifying and quantitatively analyzing P. quinquefolium.

Effects of Atrial Fibrillation-Derived Exosome Delivery of miR-107 to Human Umbilical Vein Endothelial Cells.

The aim of this study was to explore the effects of atrial fibrillation (AF)-derived exosome delivery of miR-107 to human umbilical vein endothelial cells (HUVECs) and its related mechanisms. Exosomes were isolated from the plasma of patients with AF and healthy controls, followed by characterization. The expression levels of miR-320d, miR-103a-3p, and miR-107 were measured using real-time quantitative PCR (RT-qPCR). The dual-luciferase reporter gene was used to verify the downstream target of miR-107. Afterward, HUVECs were treated with AF-derived exosomes or transfected with miR-107 mimics. After cell culture, Cell Counting Kit-8, Transwell, and flow cytometry were used to determine cell viability, migration, and apoptosis and cell cycle phase. Finally, RT-qPCR was performed to examine the expression of related genes. NanoSight, transmission electron microscopy, and western blotting showed that exosomes were successfully isolated, and that AF-derived exosomes could be taken up by HUVECs. The expression of miR-107 was significantly higher in AF-derived exosomes than in normal exosomes (p < 0.05). USP14 was shown to be the direct target of miR-107. In addition, miR-107 mimics and AF-derived exosomes significantly suppressed cell viability and migration (p < 0.05) and enhanced cell apoptosis; they also increased G0/G1-phase cells and reduced S-phase cells. RT-qPCR showed that exosomal miR-107 overexpression significantly downregulated the expression of USP14 and Bcl2 (p < 0.05), whereas it markedly upregulated the expression of ERK2, FAK, and Bax (p < 0.05). AF-derived exosomes can deliver miR-107 to HUVECs, and exosomal miR-107 may regulate cell viability, migration, and apoptosis and cell cycle progression by mediating the miR-107/USP14 pathway.

Identification of ceRNA (lncRNA-miRNA-mRNA) Regulatory Network in Myocardial Fibrosis After Acute Myocardial Infarction.

PURPOSE: Myocardial fibrosis (MF) after acute myocardial infarction (AMI) ultimately results in heart failure, which is a serious threat to human life. This study aimed to excavate critical biomarkers associated with MF after AMI. MATERIALS AND METHODS: RNA-sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in AMI and MF after AMI. RESULTS: Abundant DEmRNAs, DEmiRNAs and DElncRNAs were identified in AMI and MF after AMI. The ceRNA network, which contained 9 lncRNA-miRNA pairs and 9 miRNA-mRNA pairs, was acquired. In AMI, all candidate markers generally exhibited the same pattern as that in our RNA-seq results; while in MF after AMI, except for CENPB, JAK2 and hsa-miR-197-3p, the expression of the others in the qRT-PCR results exhibited the same pattern as that in our RNA-seq results. CONCLUSION: We speculated that LINC00664/hsa-miR-197-3p/JAK2 and GAS6-AS1/SNHG22/hsa-miR-135a-5p/CENPB/BCL9L interaction pairs may serve as potential biomarkers in MF after AMI.

miR-19a/19b-loaded exosomes in combination with mesenchymal stem cell transplantation in a preclinical model of myocardial infarction.

Aim: We aimed to investigate the protection of exogenous miR-19a/19b with bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation on cardiac function and inhibition of fibrosis in myocardial infarction (MI). Materials & methods: BM-MSC-derived exosomes were used to deliver miR-19a/19b (exo/miR-19a/19b) to the cultured cardiac HL-1 cells, and the apoptosis of cells were evaluated. Exo/miR-19a/19b and BM-MSCs were also transplanted to an in vivo MI mouse model. The recovery of cardiac function was assessed and the level of cardiac fibrosis was determined. Results: Exo/miR-19a/19b and MSCs reduced the area of cardiac fibrosis in the heart tissue in the mouse MI model. Using BM-MSC-derived exosomes as a vehicle, miR-19a/19b significantly suppressed the apoptosis of cardiac HL-1 cells. The combination of Exo/miR-19a/19b and MSC transplantation significantly enhanced the recovery of cardiac function and reduced cardiac fibrosis in the MI model. Conclusion: Our study provides an effective regenerative intervention strategy to attenuate the damage of MI.

Cardioprotective Effects of Tannic Acid on Isoproterenol-Induced Myocardial Injury in Rats: Further Insight into 'French Paradox'.

Tannic acid (TA) is a polyphenolic compound, which has shown diverse pharmacological effects with antimutagenic, anticarcinogenic and antibactericidal properties. However, cardioprotective effects of TA have not been reported. To investigate the protective effects of TA, rats were administered TA for 7 days and then intoxicated with isoproterenol (ISO). Myocardial ischemia injury was indicated by changes in electrocardiographic (ECG) patterns, morphology and cardiac marker enzymes. Furthermore, protein expression levels of c-fos, c-jun, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), cleaved-caspase-3 and -9 were analyzed by immunohistochemistry, and activities of apoptosis-related proteins Bax, Bcl-2, caspase-3 and nuclear factor kappa B (NF-κB) were detected by Western blot. Pretreatment with TA ameliorated changes in morphology and ECG, reduced activities of marker enzymes, suppressed overexpression of apoptosis-related proteins, upregulated expression of antioxidants. Moreover, TA pretreatment contributed to the decrease in ratio of Bax/Bcl-2, as well as reduced expression of TNF-α, IL-1ß, caspase-3, cleaved-caspase-3 and -9. TA displayed cardioprotective effects, which may be attributed to lowering of Bax/Bcl-2 ratio, c-fos and c-jun expression and inhibition of NF-κB activation, as well as oxidative stress, inflammation and apoptosis. These findings provide further insight into the 'French paradox' and the mechanisms underlying the beneficial effects of TA. Copyright © 2015 John Wiley & Sons, Ltd.