Background: The development of heart failure (HF) remains a common complication following an acute myocardial infarction (AMI), and is associated with substantial adverse outcomes. However, the specific predictive biomarkers and candidate therapeutic targets for post-infarction HF have not been fully established. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify key modules, hub genes, and possible regulatory targets involved in the development of HF following AMI. Methods: Genes exhibiting the most (top 50%) variation in expression levels across samples in a GSE59867 dataset were imported to the WGCNA. Gene Ontology and pathway enrichment analyses were performed on genes identified in the key module by Metascape. Gene regulatory networks were constructed using the microarray probe reannotation and bioinformatics database. Hub genes were screened out from the key module and validated using other datasets. Results: A total of 10,265 most varied genes and six modules were identified between AMI patients who developed HF within 6 months of follow-up and those who did not. Specifically, the blue module was found to be the most significantly related to the development of post-infarction HF. Functional enrichment analysis revealed that the blue module was primarily associated with the inflammatory response, immune system, and apoptosis. Seven transcriptional factors, including SPI1, ZBTB7A, IRF8, PPARG, P65, KLF4, and Fos, were identified as potential regulators of the expression of genes identified in the blue module. Further, non-coding RNAs, including miR-142-3p and LINC00537, were identified as having close interactions with genes from the blue module. A total of six hub genes (BCL3, HCK, PPIF, S100A9, SERPINA1, and TBC1D9B) were identified and validated for their predictive value in identifying future HFs. Conclusions: By using the WGCNA, we provide new insights into the underlying molecular mechanism and molecular markers correlated with HF development following an AMI, which may serve to improve risk stratification, therapeutic decisions, and prognosis prediction in AMI patients.

Objectives: Myocardial ischaemia/reperfusion (MI/R) injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanisms underlying MI/R injury are unclear. This study investigated the role of long non‐coding RNA (lncRNA) Oip5‐as1 in regulating mitochondria‐mediated apoptosis during MI/R injury.Materials and methods: Sprague‐Dawley rats were subjected to MI/R induced by ligation of the left anterior descending coronary artery followed by reperfusion. H9c2 cells were incubated under oxygen‐glucose deprivation/reoxygenation (OGD/R) conditions to mimic in vivo MI/R. RT‐qPCR and Western blot were used to evaluate gene and protein levels. CCK‐8 assay, biochemical assay and flow cytometric analysis were performed to assess the function of Oip5‐as1. The dual‐luciferase gene reporter assay and RIP assay were conducted as needed.Results: Oip5‐as1 expression was downregulated in the hearts of rats with MI/R and in H9c2 cells treated with OGD/R. Oip5‐as1 overexpression alleviated reactive oxygen species‐driven mitochondrial injury and consequently decreased apoptosis in MI/R rats and H9c2 cells exposed to OGD/R. Mechanistically, Oip5‐as1 acted as a competing endogenous RNA of miR‐29a and thus decreased its expression. Inhibition of miR‐29a reduced the oxidative stress and cytotoxicity induced by OGD/R. Overexpression of miR‐29a reversed the anti‐apoptotic effect of Oip5‐as1 in H9c2 cells treated with OGD/R. Further experiments identified SIRT1 as a downstream target of miR‐29a. Oip5‐as1 upregulated SIRT1 expression and activated the AMPK/PGC1α pathway by targeting miR‐29a, thus reducing the apoptosis triggered by OGD/R. However, these effects were reversed by a selective SIRT1 inhibitor, EX527.Conclusions: Oip5‐as1 suppresses miR‐29a leading to activation of the SIRT1/AMPK/PGC1α pathway, which attenuates mitochondria‐mediated apoptosis during MI/R injury. Our findings thus provide new insights into the molecular mechanisms of MI/R injury.

Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride–glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24–2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.

Recent studies from Europe suggest a continuing increase in thyroid cancer, but it is unclear whether this trend also applies to the United States. The current study examined the long‐term trend of thyroid cancer in Connecticut. Our results show that the overall age‐adjusted incidence rate of thyroid cancer has been increasing in Connecticut, from 1.30/100,000 in 1935–1939 to 5.78/100,000 in 1990–1992 in females, and from 0.30/100,000 in 1935–1939 to 2.77/100,000 in 1990–1992 in males. The increase mainly comes from papillary carcinoma of the thyroid. The birth cohort analyses indicate that the increase in thyroid cancer occurred among cohorts born between 1915 and 1945, which experienced an increase of 31.4% every 5 years in males and 17.3% in females over the period 1960–1979. For those born since the 1945 cohort, the incidence has been decreasing, at rates of 9.3% and 8.3% every 5 years over the period 1975–1992 in males and females, respectively. Age‐period‐cohort modeling results also suggest a strong birth cohort effect on the observed time trend in both sexes, which closely follows the introduction of radiation treatment of benign childhood conditions in the head and neck between 1920 and the 1950s in the United States. Our results are consistent with the suggested radiation hypothesis, indicating that radiation treatment of benign childhood conditions in the head and neck is largely responsible for the observed increase of thyroid cancer in Connecticut. © 1996 Wiley‐Liss, Inc.

The caspase proteins are essential for the regulation of normal B cell development and regulation of apoptosis. We investigated five single nucleotide polymorphisms in four key caspase genes, CASP3 [Ex8-280C>A (rs6948) and Ex8+567T>C (rs1049216)], CASP8 Ex14-271A>T (rs13113), CASP9 Ex5+32G>A (rs1052576) and CASP10 Ex3-171A>G (rs3900115) to determine whether they alter risk for non-Hodgkin lymphoma (NHL) in a population-based case–control study of women in Connecticut (461 cases and 535 controls). Variants in CASP3 and CASP9 were significantly associated with a decreased risk for NHL, particularly follicular lymphoma [e.g. CASP3 Ex8+567T>C odds ratio (OR) _CC+TC = 0.4, 95% confidence interval (CI) = 0.3–0.7; and CASP9 Ex5+32G>A OR _AA+AG = 0.6, 95% CI = 0.4–1.0]. Further, variants in CASP3, CASP8 and CASP10 were associated with a decreased risk of marginal zone lymphoma and variants in CASP3 and CASP10 were associated with a lower risk of chronic lymphocytic leukemia and related subtypes. The striking protective associations observed for polymorphisms in all four genes for NHL and/or one or more subtypes suggest that genetic variation in CASP genes may play an important role in the etiology of NHL.