Diabetic cardiomyopathy (DCM) is a pathophysiological condition induced by diabetes mellitus that often causes heart failure (HF). However, their mechanistic relationships remain unclear. This study aimed to identify immune gene signatures and molecular mechanisms of DCM. Microarray data from the Gene Expression Omnibus (GEO) database from patients with DCM were subjected to weighted gene co-expression network analysis (WGCNA) identify co-expression modules. Core expression modules were intersected with the immune gene database. We analyzed and mapped protein-protein interaction (PPI) networks using the STRING database and MCODE and filtering out 17 hub genes using cytoHubba software. Finally, potential transcriptional regulatory factors and therapeutic drugs were identified and molecular docking between gene targets and small molecules was performed. We identified five potential immune biomarkers: proteosome subunit beta type-8 (PSMB8), nuclear factor kappa B1 (NFKB1), albumin (ALB), endothelin 1 (EDN1), and estrogen receptor 1 (ESR1). Their expression levels in animal models were consistent with the changes observed in the datasets. EDN1 showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR) and Western blotting(WB). Subsequently, we confirmed that the potential transcription factors upstream of EDN1 were PRDM5 and KLF4, as its expression was positively correlated with the expression of the two transcription factors. To repurpose known therapeutic drugs, a connectivity map (CMap) database was retrieved, and nine candidate compounds were identified. Finally, molecular docking simulations of the proteins encoded by the five genes with small-molecule drugs were performed. Our data suggest that EDN1 may play a key role in the development of DCM and is a potential DCM biomarker.

Carotenoid levels are inversely associated with blood pressure (BP). This study focused on the effects of individual and combined serum carotenoids on BP and hypertension, which have not been established to date. Data from National Health and Nutrition Examination Survey (NHANES) 2001–2006 were analyzed in this cross-sectional study. Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were applied to explore the associations of six serum carotenoids (α-carotene, β-cryptoxanthin, lutein/zeaxanthin, trans-lycopene, trans-β-carotene, and cis-β-carotene), individually and in combination, with BP/hypertension. The linearity of correlations was further assessed using restricted cubic spline (RCS) regression. A total of 11,336 adults were included for analysis. Data from multivariate models showed that all six carotenoids were independently and negatively associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP; all p < 0.05). Compared to the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.64 [0.52–0.77]), β-cryptoxanthin (OR = 0.74 [0.60–0.90]), trans-β-carotene (OR = 0.50 [0.40–0.61]), and cis-β-carotene (OR = 0.47 [0.35–0.64]) were significantly and inversely related to hypertension (all p < 0.05). Moreover, WQS analysis revealed that the combination of all six serum carotenoids was negatively associated with BP and hypertension (all P<0.001), among which trans-β-carotene was the most significant contributor to the protective effect against hypertension (weight, 59.50%). Dose-response analyses demonstrated a linear inverse association of all carotenoids with hypertension (p for non-linearity > 0.05). Our collective findings indicate that higher levels of all six mixed serum carotenoids are correlated with decreased prevalence of hypertension, among which β-carotene exerts the most significant effect, which may provide a basis and direction for further studies.

Background Early reperfusion of the coronary artery has become the first choice for patients with ST-segment elevation myocardial infarction (STEMI). How to deal with patients who miss the time window for early reperfusion is still controversial. Based on real-world data, this study was conducted to explore whether percutaneous coronary intervention (PCI) has an advantage over standard drug therapy in patients who miss the optimal treatment window. Methods Consecutive patients who were diagnosed with STEMI and met the inclusion criteria between 2009 and 2018 in our center were retrospectively included in this cohort study. The primary endpoint events were major adverse cardiac events (MACEs), including heart failure, sudden cardiac death, malignant arrhythmia, thrombi and bleeding events during the period of admission. Secondary endpoint events were components of MACEs. At the same time, we also evaluated angina pectoris at admission and discharge through Canadian Cardiovascular Society (CCS) grading. Results This study enrolled 417 STEMI patients and divided them into four groups (PCI < 3 days, 14.87%; 3 days<PCI < 7 days, 21.104%; PCI > 7 days, 34.29%; MED, 29.74%). During the period of admission, MACEs occurred in 52 cases. The incidence of MACEs was 11.29, 7.95, 4.20 and 25.81% in the four respective groups (p < 0.0001). The MED group had higher rates of MACEs (OR = 3.074; 95% CI 0.1.116–8.469, p = 0.03) and cardiac death (OR = 3.027; 95% CI 1.121–8.169, p = 0.029) compared to the PCI group. Although both treatments were effective in improving CCS grade at discharge, the PCI group improved more significantly (p < 0.0001). Conclusions In the real world, delayed PCI can be more effective in patients with angina symptoms at discharge and reduce the incidence of MACEs and cardiac death during hospitalization. The timing of intervention was independent of the occurrence of MACEs during hospitalization and of improvement in symptoms.