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Background. Septic cardiomyopathy (SC) is characterized by myocardial dysfunction caused by sepsis and constitutes one of the serious complications of sepsis. Pyroptosis is a unique proinflammatory programmed cell death process. However, the role of pyroptosis in the development of SC remains unclear, and further study is required. The purpose of this study is to identify pyroptosis-related genes (PRGs) in SC and explore the mechanism of pyroptosis involved in the regulation of SC formation and progression. Methods. Differential expression analysis and enrichment analysis were performed on the SC-related dataset GSE79962 to identify differentially expressed genes (DEGs). PRGs were screened by intersecting genes associated with pyroptosis in previous studies with the DEGs obtained from GSE79962. The expression pattern of them was studied based on their raw expression data. Additionally, corresponding online databases were used to predict miRNAs, transcription factors (TFs) and therapeutic agents of PRGs. Lipopolysaccharide (LPS)-induced cell damage models in H9C2 and AC16 cell lines were constructed, cell activity was detected by CCK-8 and cell pyroptosis were detected by Hoechst33342/PI staining. Furthermore, these PRGs were verified in the external datasets (GSE53007 and GSE142615) and LPS-induced cell damage model. Finally, the effect of siRNA-mediated PRGs knockdown on the pyroptosis phenotype was examined. Results. A total of 1,206 DEGs were screened, consisting of 663 high-expressed genes and 543 low-expressed genes. Among them, ten PRGs (SOD2, GJA1, TIMP3, TAP1, TIMP1, NOD1, TP53, CPTP, CASP1 and SAT1) were identified, and they were mainly enriched in "Pyroptosis'', "Ferroptosis'', "Longevity regulating pathway'', and "NOD-like receptor signaling pathway''. A total of 147 miRNAs, 31 TFs and 13 therapeutic drugs were predicted targeting the PRGs. The expression trends of SOD2 were confirmed in both the external datasets and LPS-induced cell damage models. Knockdown of SOD2 induced increased pyroptosis in the AC16 LPS-induced cell damage model. Conclusions. In this study, we demonstrated that SOD2 is highly expressed in both the SC and LPS-induced cell damage models. Knockdown of SOD2 led to a significant increase in pyroptosis in the AC16 LPS-induced cell damage model. These findings suggest that SOD2 may serve as a potential target for the diagnosis and treatment of SC. [ABSTRACT FROM AUTHOR]

Context: Carnitine has been associated with cardiac energy metabolism and heart failure, but the association between its precursors--trimethyllysine (TML) and γ-butyrobetaine (GBB)--and heart failure with preserved ejection fraction (HFpEF) remains unclear. Objective: To evaluate the relationship between TML-related metabolites and HFpEF in an Asian population. Methods: The cross-sectional component of this study examined the association between plasma TML-related metabolites and HFpEF, while a prospective cohort design was applied to examine the association with incident cardiovascular events in HFpEF. Included in the study were 1000 individuals who did not have heart failure (non-HF) and 1413 patients with HFpEF. Liquid chromatography mass spectrometry was used to assess plasma carnitine, GBB, TML and trimethylamine-N-oxide (TMAO) concentrations. Results: Plasma GBB and TML were both elevated in patients with HFpEF. After adjusting for traditional risk factors and renal function, TML, but not GBB, was significantly associated with HFpEF. The odds ratio (OR) for the fourth vs first quartile of TML was 1.57 (95% CI 1.09-2.27; P-trend<.01). The OR for each SD increment of log-TML was 1.26 (95% CI 1.08-1.47). Plasma TMAO (P-interaction=0.024) and estimated glomerular filtration rate (P-interaction=0.024) modified the TML-HFpEF association. The addition of TML improved the diagnostic value under the multivariable model. In the prospective study of patients with HFpEF, higher plasma TML was associated with increased risk of cardiovascular events. Conclusion: Plasma TML concentrations are positively associated with HFpEF, and higher plasma TML indicates increased risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has induced an ongoing global health crisis. Here we utilized a combination of targeted amino acids (AAs) and clinical biochemical profiling to analyze the plasma of coronavirus disease 2019 (COVID-19) subjects at the hospitalization stage and 1-month post-infection convalescent stage, respectively, to investigate the systematic injury during COVID-19 disease progress. We found the virus-induced inflammatory status and reduced liver synthesis capacity in hospitalized patients, whichmanifested with increased branched-chain AAs (BCAAs), aromatic AAs (AAAs), one-carbon related metabolites, and decreased methionine. Most of these disturbances during infection recover except for the increased levels of medium-chain acylcarnitines (ACs) in the convalescent subjects, implying the existence of incomplete fatty acids oxidation during recovery periods. Our results suggested that the imbalance of the AA profiling in COVID-19 patients. The majority of disturbed AAs recovered in 1 month. The incomplete fatty acid oxidation products suggested it might take longer time for convalescent patients to get complete recovery. [ABSTRACT FROM AUTHOR]