Identification of key proteins as potential biomarkers associated with post-infarction complications in diabetics.

Background: The ability of transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction in diabetic patients remains unknown. The present study was designed to detect possible biomarkers associated with the incidence of post-infarction complications in diabetes to assist thedevelopment of novel treatments for this condition.Methods: Two gene expression datasets, GSE12639 and GSE6880, were downloaded from the Gene Expression Omnibus (GEO) database, and then differentially expressed genes (DEGs) were identified between post-infarction diabetics and healthy samples from the left ventricular wall of rats. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed to explore the functional roles of these genes.Results: In total, 30 DEGs (14 upregulated and 16 downregulated) were shared between these two datasets, as identified through Venn diagram analyses. GO analyses revealed these DEGs to be significantly enriched in ovarian steroidogenesis, fatty acid elongation, biosynthesis of unsaturated fatty acids, synthesis and degradation of ketone bodies, and butanoate metabolism. The PPI network of the DEGs had 14 genes and 70 edges. We identified two key proteins, 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2) and Δ3, Δ2-Enoyl-CoA Delta Isomerase 1 (ECI1), and the upregulated gene Hmgcs2 with the highest score in the MCC method. We generated a co-expression network for the hub genes and obtained the top ten medications suggested for infarction with diabetes.Conclusion: Taken together, the findings of these bioinformatics analyses identified key hub genes associated with the development of myocardial infarction in diabetics. These hub genes and potential drugs may become novel biomarkers for prognosis and precision treatment in the future.

Extracellular Vesicles and Vascular Inflammation.

Vascular inflammation is the most common pathological feature in the pathogenesis of human disease. It is a complex immune process involved with many different types of cells including platelet, monocytes, macrophages, endothelial cells, and others. It is widely accepted that both innate and adaptive immune responses are important for the initiation and progression of vascular inflammation. The cell-cell interaction constitutes an important aspect of those immune responses in the vascular inflammation. Extracellular vesicles (EVs) are nanometer-sized double-layer lipid membrane vesicles released from most types of cells. They have been proved to play critical roles in intercellular communication in the occurrence and development of multisystem diseases. With the advancement of basal medical science, the biological roles of EVs in vascular inflammation have been clearer today. In this chapter, we will summarize the advance progress of extracellular vesicles in regulating vascular inflammation and its potential application in the clinical.

Response of Juvenile Saccharina japonica to the Combined Stressors of Elevated pCO2 and Excess Copper.

Coastal macroalgae may be subjected to global and local environmental stressors, such as ocean acidification and heavy-metal pollution. We investigated the growth, photosynthetic characteristics, and biochemical compositions of juvenile sporophytes of Saccharina japonica cultivated at two pCO2 levels (400 and 1000 ppmv) and four copper concentrations (natural seawater, control; 0.2 µM, low level; 0.5 µM, medium level; and 1 µM, high level) to better understand how macroalgae respond to ongoing environmental changes. The results showed that the responses of juvenile S. japonica to copper concentrations depended on the pCO2 level. Under the 400 ppmv condition, medium and high copper concentrations significantly decreased the relative growth rate (RGR) and non-photochemical quenching (NPQ) but increased the relative electron transfer rate (rETR) and chlorophyll a (Chl a), chlorophyll c (Chl c), carotenoid (Car), and soluble carbohydrate contents. At 1000 ppmv, however, none of the parameters had significant differences between the different copper concentrations. Our data suggest that excess copper may inhibit the growth of juvenile sporophytes of S. japonica, but this negative effect could be alleviated by CO2-induced ocean acidification.

Human umbilical cord mesenchymal stem cells ameliorate depression by regulating Jmjd3 and microglia polarization in myocardial infarction mice.

RATIONALE: Microglia regulate the inflammation of the central nervous system and play a crucial role in the pathogenesis of depression. Moreover, Jmjd3 is involved in microglia polarization. Mounting studies reported the beneficial effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on myocardial infarction (MI), Unfortunately, its effects on MI-induced depression and its underlying mechanisms remain unclear. OBJECTIVES: We aimed to investigate the antidepressant effects of HUC-MSCs and their impacts on microglia polarization. METHODS: In the current study, the MI model was established by ligating the left anterior descending coronary artery. Mice were injected with HUC-MSCs or PBS through the tail vein 1week after the surgery. The sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were performed to evaluate depression-like behavior. Cardiac function and myocardial fibrosis were evaluated at the end of the experiments. Immunofluorescence, Western blot, ELISA, and qRT-PCR were used to detect the levels of Jmjd3 and microglia-related markers and inflammatory factors. RESULTS: HUC-MSC treatment significantly improved cardiac function, reduced the area of myocardial fibrosis, and alleviated depression-like behaviors induced by MI. HUC-MSCs inhibited the expression of Jmjd3 and promoted the switch of microglia in the prefrontal cortex, hypothalamus, and hippocampus from M1 to M2, thereby decreased the level of pro-inflammatory factors. CONCLUSION: HUC-MSCs have cardioprotective and potential anti-depressive effects induced by MI related to the inflammation improved by regulating Jmjd3 and microglial polarization.

The impact of the Type D Personality pattern on prehospital delay in patients suffering from acute myocardial infarction.

BACKGROUND: The Type D Personality (TDP) has been specifically linked to acute myocardial infarction (AMI). However, the impact on prehospital delay of AMI patients is unclear. The aim of this study was to assess the relationship between TDP and pre-hospital delay time (PHT) in a Chinese population. METHODS: A total of 256 AMI patients (47 women and 209 men) were taken from the Multicenter Delay in Patients Experiencing AMI in Shanghai (MEDEA FAR-EAST) study. Sociodemographic and psycho-behavioral characteristics were assessed by bedside interviews and questionnaires. TDP was evaluated according to the Type D Personality Scale (DS14) subdivided in social inhibition (SI) and negative affectivity (NA). Based on a significant interaction analysis of TDP and sex on PHT, all analyses were stratified by sex. RESULTS: PHT of female patients with TDP were substantially shorter compared to non-TDP female patients (108 vs. 281 min, P=0.029). In male patients, no effect of TDT on PHT was found. Spearman correlation analysis suggests that NA was negatively correlated with PHT (r=-0.358, P=0.014). Further age-adjusted logistic regression analyses showed that female patients with TDP were generally less likely to prehospital delay compared with non-TDP patients (OR =0.28; 95% CI, 0.08-0.98) and had a lower risk of PHT >360 minutes (OR =0.10; 95% CI, 0.01-0.91). However, statistical significance disappeared after adjustment for psychological factors (anxiety, depression, suboptimal wellbeing, cardiac denial and stress event). CONCLUSIONS: TDP is associated with less prehospital delay in female patients during AMI-an effect which may be particularly mediated by NA.

The MEDEA FAR-EAST Study: Conceptual framework, methods and first findings of a multicenter cross-sectional observational study.

BACKGROUND: The substantial increase in cardiovascular diseases (CVD) in China over the last three decades warrants comprehensive preventive primary and secondary strategies. Prolonged prehospital delay (PHD) has been identified as a substantial barrier to timely therapeutic interventions for acute myocardial infarction (AMI). Despite worldwide efforts to decrease the patient's decision-making time, minimal change has been achieved so far. Here, we aim to describe the conceptual framework and methods and outline key data of the MEDEA FAR-EAST Study, which aimed to elucidate in-depth barriers contributing to delay in Chinese AMI-patients. METHODS: Data sources of this multicenter cross-sectional observational study are a standardized bedside interview, a self-administered tailored questionnaire tool and the patient chart. PHD was defined as the main outcome and triangulated at bedside. Standard operation procedures ensured uniform data collection by trained study personnel. The study was ethically approved by Tongji-Hospital and applied to all participating hospitals. RESULTS: Among 379 consecutively screened patients, 296 (78.1%) fulfilled eligibility criteria. A total of 241 (81.4%) AMI-patients were male and 55 (18.6%) female. Mean age was 62.9 years. Prehospital delay time was assessed for 294 (99.3%) patients. Overall median PHD was 151 min with no significant sex difference. Symptom mismatch was present in 200 (69.7%) patients and 106 (39.0%) patients did not attribute their symptoms to cardiac origin. A total of 33 (12.4%) patients suffered from depression, 31 (11.7%) from anxiety and 141 (53.2%) patients employed denial as their major coping style. CONCLUSION: This is the first study on prehospital delay with emphasis on psychological variables in Chinese AMI-patients. A comprehensive assessment tool to measure clinical and psychological factors was successfully implemented. Socio-demographic key data proved a good fit into preexisting Chinese literature. Potential barriers including cardiac denial and symptom-mismatch were assessed for the first time in Chinese AMI-patients. The pretested selection of instruments allows future in depth investigations into barriers to delay of Chinese AMI-patients and enables inter-cultural comparisons.

The role of immune abnormality in depression and cardiovascular disease.

Depression and cardiovascular disease (CVD) are both highly prevalent disorders, and some evidence shows that there is a 'vicious cycle' linking major depression and CVD. There is also growing evidence that immune abnormalities underpin the common pathophysiology of both CVD and major depression. The abnormalities include the following: abnormal levels of inflammatory markers, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and interleukin-12 (IL-12); increased acute phase proteins, such as C-reactive protein, fibrinogen and haptoglobin; and abnormal complement factors. The findings show that major depression and CVD patients have greater immune abnormalities, which may increase depressive symptoms and cardiovascular pathological changes, and that there may be a bidirectional relationship, therefore more prospective studies are needed to draw conclusions.

Statin Function as an Anti-inflammation Therapy for Depression in Patients With Coronary Artery Disease by Downregulating Interleukin-1ß.

It is well known that inflammation contributes to the development of coronary artery disease (CAD) and depressive symptoms. Previous studies have shown that long-term application of statin reduces the occurrence of depression in patients with CAD. However, the mechanism remains unclear. We hypothesized that inflammation contributes to depression in patients with CAD and statin function as an anti-inflammation therapy for those depressive patients. Patients with confirmed CAD hospitalized in the Department of Cardiology of Tongji Hospital in Shanghai, China, were enrolled. Depression was identified as none (ND), mild (MiD), moderate (MoD), or severe (SD) on the basis of scores of the patient health questionnaire with 9 items. Inflammatory factors in peripheral blood were measured using a chemiluminescence immunoassay and Bio-plex. Luciferase expression level was detected using the Dual-Luciferase Reporter Assay System for IL-1ß or NF-κB expression by transfection in human umbilical vein endothelial cells, and patient serum was added. Data obtained from 217 patients with CAD were analyzed. The IL-1ß level of CAD with SD was 14.70, which was significantly higher than that of CAD with ND 7.52, MiD 7.73, or MoD 8.63. Luciferase reporter gene analysis showed that IL-1ß or NF-κB expression level was upregulated by the serum of CAD and depression patients. After the addition of atorvastatin, IL-1ß or NF-κB luciferase reporter expression level decreased. It suggested that depression in patients with CAD is associated with inflammation. Statin may function as an anti-inflammation therapy for depression in patients with CAD by downregulation of IL-1ß.