Background and Objective: Heart failure (HF) is a global public health problem with high morbidity, readmission, and mortality rates. The central mediators of cardiomyocyte survival and death are mitochondria. Mitochondria are a key therapeutic target for HF and are closely involved in the pathophysiological process of HF. A recent study proposes that cuproptosis, a novel cell death mechanism, is closely related to mitochondrial respiration. Therefore, this study aims to explore the link between cuproptosis and HF, and to find novel therapeutic targets and treatments for HF.Methods: A literature search (up to April 2022) was conducted through PubMed database, and the search range was limited to publications in English. After further literature search and screening, we found that we are currently the first study to explore the association between HF and cuproptosis.

Background D-dimer level can reflect the hypercoagulable state of atrial fibrillation (AF) and predict thromboembolic events. However, no effective indicator associated with D-dimer of AF patients has been found to prevent thromboembolic events in AF. This retrospective study from a single center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm. Material/Methods A total of 909 NVAF patients and 653 sex- and age-matched sinus rhythm participants were used to compare serum albumin and D-dimer levels. Serum albumin was determined by colorimetry, and D-dimer level was determined by latex-enhanced photoimmunoassay. We analyzed the correlation of serum albumin and D-dimer with NVAF by correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve. Results Albumin ( P <0.001) and D-dimer ( P <0.001) were significantly associated with NVAF. Among NVAF patients, D-dimer level was negatively correlated with albumin levels ( P <0.001), and albumin level was an independent risk factor of abnormal D-dimer level (>0.5 ug/mL), which was also an effective predictor of abnormal D-dimer level (the area under the ROC curve was 0.77, P <0.001), and the optimal cutoff value was 36.95 g/L. Conclusions Serum albumin and D-dimer levels were significantly associated with NVAF. In NVAF patients, D-dimer level was inversely correlated with albumin levels, and albumin level was an independent risk factor and effective predictor of abnormal D-dimer level. Close examination and supplementation of serum albumin can prevent thromboembolic events, but further clinical research and confirmation are needed.

Objective. Coronary heart disease (CHD) is the leading cause of death from cardiovascular disease and has become an important public health problem worldwide. Guizhi Gancao Decoction (GGD) has been shown to be used in the treatment of CHD with good efficacy, but its specific therapeutic mechanism and active ingredients have not been fully clarified. This study aims to identify the active compounds and key targets of GGD in the treatment of CHD, explore the therapeutic mechanism of GGD, and provide candidate compounds for anti-CHD drug development. Methods. The main compounds of GGD were determined by UPLC-MS/MS analysis and screened by SwissADME. The corresponding targets of GGD compounds were obtained from SwissTargetPrediction, and the targets of CHD were obtained from the HERB and GeneCards databases. The STRING 11.5 database was used to analyze the PPI (Protein-Protein Interactions) network of potential therapeutic targets of GGD compounds. Cytoscape 3.7.2 was used to construct target-related networks and find core targets. The GEO database was used to validate the differential expression of core targets. The PANTHER Classification System was used to functionally classify potential therapeutic targets for GGD. The GO biological process analysis and KEGG pathway analysis of targets were completed by DAVID 6.8 database. AutoDockTools 1.5.6 and PyMol 2.5.2 were used to perform molecular docking of core targets with the active GGD compounds. Results. 7 active GGD compounds were obtained based on UPLC-MS/MS and pharmacological parameter evaluation, which corresponded to 131 CHD-related targets. Among them, EGFR, MAPK3, RELA, CCND1, ESR1, PTGS2, NR3C1, CYP3A4, MMP9, and PTPN11 were considered core targets. According to the targets related to CHD, glycyrrhetinic acid, liquiritigenin, and schisandrin are considered key active ingredients. GO biological process and KEGG analysis indicated that the potential targets of GGD in the treatment of CHD involve a variety of biological processes and therapeutic mechanisms. Molecular docking results showed that both the core targets and the corresponding compounds had the good binding ability. Conclusions. This study contributes to a more comprehensive understanding of the therapeutic mechanism and active ingredients of GGD for CHD and provides candidate compounds for drug development of CHD.

At present, although the early treatment of sepsis is advocated, the treatment effect of sepsis is unsatisfactory, and the mortality rate remains high. Shenfu injection (SFI) has been used to treat sepsis with good clinical efficacy. Based on network pharmacology, this study adopted a new research strategy to identify the potential therapeutic targets and key active ingredients of SFI for sepsis from the perspective of the pathophysiology of sepsis. This analysis identified 28 active ingredients of SFI based on UHPLC-QQQ MS, including 18 ginsenosides and 10 aconite alkaloids. 59 targets were associated with the glycocalyx and sepsis pathways. Based on the number of targets related to the pathophysiological process of sepsis, we identified songorine, ginsenoside Rf, ginsenoside Re, and karacoline as the key active ingredients of SFI for the treatment of sepsis. According to the cluster analysis of MCODE and the validation on the GEO dataset, LGALS3, BCHE, AKT1, and IL2 were identified as the core targets. This study further explored the therapeutic mechanism and the key active ingredients of SFI in sepsis and provided candidate compounds for drug development.

Shixiao powder comes from the Formularies of the Bureau of People’s Welfare Pharmacies in the Song Dynasty and consists of two herbs, Puhuang (PH) and Wulingzhi (WLZ). PH-WLZ is a commonly used drug pair for the treatment of coronary heart disease (CHD), and its clinical effect is remarkable. However, our understanding of the mechanism of treatment of CHD is still unclear. In this study, the method of network pharmacology was used to explore the mechanism of PH-WLZ in the treatment of CHD. A total of 56 active ingredients were identified from PH-WLZ, of which 93 targets of 41 active ingredients overlapped with those of CHD. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with CHD and those associated with the mechanism of PH-WLZ in the treatment of CHD. By constructing the protein-protein interaction (PPI) network of common targets, 10 hub genes were identified. Based on the number of hub genes contained in the enrichment analysis, we obtained the key pathways of PH-WLZ in the treatment of CHD. The key KEGG pathway in the treatment of CHD by PH-WLZ is mainly enriched in atherosclerosis, inflammation, immunity, oxidative stress, and infection-related pathways. Moreover, the results of molecular docking showed that the active ingredients of PH-WLZ had a good affinity with the hub genes. The results indicate that the mechanism of PH-WLZ in the treatment of CHD may be related to regulation of lipid metabolism, regulation of immune and inflammatory responses, regulation of downstream genes of fluid shear stress, antiaging and oxidative stress, and virus inhibition.