6‐Gingerol (6‐G) is known to alleviate myocardial ischemia/reperfusion injury. However, the underlying molecular mechanisms of 6‐G myocardial protection are not known. In this study, the protective effect of 6‐G on ischemia/reperfusion (I/R) damage and whether such a mechanism was related to apoptosis inhibition and activation of phosphoinositide 3‐kinases (PI3K)/serine/threonine kinase (Akt) signaling pathway were investigated. Rats were subjected to I/R in the presence or absence of 6‐G and the changes of cardiac function, infarct size and histopathological changes, and the levels of cardiac troponin T, creatine kinase‐MB, and myocardial apoptosis were examined. The expression of caspase‐3, PI3K, p‐Akt, and Akt was also determined. We found that 6‐G (6 mg/kg) pretreatment significantly improved heart function and ameliorated infarct size and histopathological changes and cardiac troponin T and creatine kinase‐MB levels induced by I/R. Moreover, pretreatment with 6‐G significantly inhibited myocardial apoptosis and caspase‐3 activation induced by I/R. 6‐G also upregulated expression of PI3K, p‐Akt, and Akt in myocardial tissues. Taken together, these findings suggest that 6‐G inhibits apoptosis and activates PI3K/Akt signaling in response to myocardial I/R injury as a possible mechanism to attenuate I/R‐induced injury in heart. These results might be important for developing novel strategies for preventing myocardial I/R injury.

BACKGROUND:With the increasing research on non-alcoholic fatty liver (NAFLD) and acute myocardial infarction (AMI), many evidences show a tight correlation between NAFLD and AMI, however the underlying pathophysiology is still not clear. This study was to identify the potential hub genes and pathways related to these two diseases via bioinformatic method. MATERIAL AND METHODS:Gene Expression Omnibus (GEO) dataset GSE63067 of NAFLD patients and normal controls was downloaded from GEO database. The GSE60993 and GSE66360 datasets for AMI patients and healthy controls were also obtained. Differential expression genes (DEGs) of NAFLD and AMI datasets, accompanied with common genes between them were achieved. Further GO and KEGG enrichment analysis for common genes were performed. RESULTS:To obtain the pathogenesis associated with both NAFLD and AMI, protein-protein interaction (PPI) network was constructed and the top ten hub genes (TLR2, LILRB2, CXCL1, FPR1, TLR4, TYROBP, MMP9, FCER1G, CLEC4D and CCR2) were selected with CONCLUSIONS:The results of this study suggesting some novel genes may play an important role in the occurrence and progression NAFLD and AMI. But more experimental researches and clinical trials need to verify.

Background: Atrial fibrillation (AF) is the most common persistent arrhythmia. Valvular heart disease (VHD) and AF frequently coexist. In our study, from performing bioinformatics analysis, we sought to identify immune-related genes (IRGs) and explore the role of immune cell infiltration in AF-VHD in depth, aiming at investigating the potential molecular mechanism and developing new therapeutic targets for AF, including AF-VHD. Methods: The gene expression of the GSE41177 and GSE79768 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed via the limma package in Bioconductor with R software. Differentially expressed immune-related genes (DEIRGs) were selected via combination ImmPort database with DEGs, and the enrichment function and pathway analysis were explored. A protein-protein interaction (PPI) network was built with a Search Tool for the Retrieval of Interacting Genes/Proteins plugin in Cytoscape. The CIBERSORT algorithm was used to evaluate immune infiltration in the left atrial (LA) tissues between AF-VHD and sinus rhythm (SR) patients. Finally, a correlation analysis between key DEIRGs and infiltrating immune cells was performed. Results: A total of 130 DEIRGs were detected. Enrichment function of DEIRGs demonstrated that they are significant in immune and inflammatory responses. The key DEIRGs assessed by the PPI network and involved in both the immune and inflammatory responses were the C-X-C motif chemokine ligand (CXCL) 1, pro-platelet basic protein (PPBP), CXCL12, and C-C motif chemokine ligand 4 (CCL4). The immune infiltration findings indicated that, compared with the LA tissues from SR patients, the tissues from AF-VHD patients contained a higher proportion of gamma delta T cells, but a lower proportion of CD8 and regulatory T cells. The results of correlation analysis demonstrated that CXCL1 was positively correlated with activated mast cells and significantly negatively correlated with resting mast cells. PPBP, CXCL12, and CCL4 were positively correlated with the infiltration of various immune cells, such as neutrophils, plasma cells, and resting dendritic cells. Conclusions: The key immune-related genes and the differences in immune infiltration in LA tissues play an essential role in the occurrence and progression of AF-VHD.

Background and aims: inflammation plays an important role in atrial fibrillation (AF). In this study, we investigated the significance of immune cell infiltration in AF and identified the potential Hub genes involved in the regulation of immune cell infiltration in AF.Methods: we obtained AF datasets from the GEO database and analyzed them for obtaining differentially expressed genes (DEGs) by R software. Then, we performed GO, KEGG, and GSEA enrichment analyses of DEGs. The Hub genes of AF were determined by least absolute shrinkage selection operator (LASSO) regression analysis and weighted gene co-expression network analysis (WGCNA). Their validation was verified by using quantitative polymerase chain reaction (qPCR) in the AF rat model. Finally, we used a single sample GSEA (ssGSEA) to analyze immune cell infiltration and its relationship with hub genes.Results: We obtained 298 DGEs from the heatmap and found that DGEs were closely related to inflammation, immunity, and cytokine interactions by enrichment analyses. We obtained 10 co-expression modules by WGCNA. Among them, the module including CLEC4A, COTL1, EVI2B, FCER1G, GAPT, HCST, NCF2, PILRA, TLR8, and TYROBP had the highest correlation with AF. Four Hub genes (PILRA, NCF2, EVI2B, GAPT) were obtained further by LASSO analysis. The results suggested that the expression level of PILRA was significantly elevated in the rats with AF by qPCR, compared to the rats without AF. The results revealed that the infiltration of neutrophils, macrophages, monocytes, mast cells, immature B cells, myeloid-derived suppressor cell (MDSC), dendritic cell, and T cells and their partial subpopulations were closely related to AF by ssGSEA analysis, and PILRA was positively correlated with immature B cell, monocyte, macrophage, mast cell, dendritic cell, and T cells and their partial subpopulations by Spearman correlation analysis.Conclusions: PILRA was closely related to multiple types of immune cell infiltration, which may be associated with AF. PILRA may be a novel target of intervention for AF.

BACKGROUND Osteoporosis is a metabolic osteopathy characterized by abnormal bone mass and microstructure that has become a public health problem worldwide. Cuscutae semen (CS) is a traditional Chinese medicine (TCM) that has a positive effect on the prevention and treatment of osteoporosis. However, the mechanism of CS is unclear. Therefore, this study aimed to reveal the possible molecular mechanism involved in the effects of CS on osteoporosis based on a network pharmacology approach. MATERIAL AND METHODS The inactive and active ingredients of CS were identified by searching the pharmacology analysis platform of the Chinese medicine system (TCMSP), and the targets of osteoporosis were screened in the relevant databases, such as GeneCards, PubMed, and the Comparative Toxicogenomics Database (CTD). The network of "medicine-ingredients-disease-targets (M-I-D-T)" was established by means of network pharmacology, and the key targets and core pathways were determined by R analysis. Molecular docking methods were used to evaluate the binding activity between the target and the active ingredients of CS. RESULTS Eleven active ingredients were identified in CS, and 175 potential targets of the active ingredients were also identified from the TCMSP. Moreover, we revealed 22 539 targets related to osteoporosis in the 3 well-established databases, and we determined the intersection of the disease targets and the potential targets of the active ingredients; 107 common targets were identified and used in further analysis. Additionally, biological processes and signaling pathways involved in target action, such as fluid shear stress, atherosclerosis, cancer pathways, and the TNF signaling pathway, were determined. Finally, we chose the top 5 common targets, CCND1, EGFR, IL6, MAPK8, and VEGFA, for molecular docking with the 11 active ingredients of CS. CONCLUSIONS This study suggested that CS has multiple ingredients and multiple targets relevant to the treatment of osteoporosis. We determined that the active ingredient, sesamin, may be the most crucial ingredient of CS for the treatment of osteoporosis. Additionally, the network pharmacology method provided a novel research approach to analyze the function of complex ingredients.

Several studies have indicated that long noncoding RNAs (lncRNAs)-HOX transcript antisense RNA (HOTAIR) is involved in some cardiovascular diseases by regulating gene expression as a competitive endogenous RNA (ceRNA). GJA1 encoding Cx43 is one potential target gene of microRNA-613 (miR-613). Meanwhile, there is a potential target regulatory relationship between HOTAIR and miR-613. The present study is aimed at investigating whether HOTAIR functions as a ceRNA to regulate the Cx43 expression in atrial fibrillation (AF) by sponging miR-613. The expressions of HOTAIR, miR-613, and Cx43 were detected in the right atrial appendages of 45 patients with heart valve disease, including 23 patients with chronic AF. The HOTAIR overexpressed and underexpressed HL-1 cell model were constructed to confirm the effect of HOTAIR on Cx43. Then, the Cx43 expression was detected to testify the interplay between HOTAIR and miR-613 after cotransfecting HOTAIR and miR-613. Furthermore, luciferase assays were performed to verify that HOTAIR could regulate Cx43 remolding as a ceRNA by sponging miR-613. The expression of HOTAIR and Cx43 was significantly downregulated in chronic AF group. HOTAIR regulated positively the Cx43 expression in HL-1 cells. The upregulated effect of HOTAIR on the Cx43 expression could be remarkably attenuated by miR-613. Moreover, the inhibitory effect of miR-613 on the Cx43 expression could be obviously mitigated by HOTAIR. At last, luciferase assays confirmed HOTAIR functioned as a ceRNA in the Cx43 expression by sponging miR-613. Our study suggests that HOTAIR, functioning as a ceRNA by sponging miR-613, is an important contributor to Cx43 remolding in AF.