Investigation of the Potential Key Genes and the Multitarget Mechanisms of Polygonum cuspidatum against Heart Failure Based on Network Pharmacology and Experimental Validation.

In this study, systematic pharmacology and bioinformatic approaches were employed to identify the potential targets of Polygonum cuspidatum (PC) for treating heart failure (HF). The active ingredients of PC were screened by using the TCMSP database, and HF-related genes were identified in the GEO database. Then, the herb-HF targeted-gene networks were constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were performed to obtain the enriched molecular pathways associated with the pathogenesis of HF. Finally, in vitro experiment was performed to evidence network pharmacology analysis. 170 intersection genes were obtained, and key genes (FOXO3, NFKB1, and TNF) were identified. Besides, GO and KEGG findings indicated that PC treatment of HF was achieved via regulating apoptosis, IL-17 signaling pathway, TNF signaling pathway, response to oxidative stress, and response to reactive oxygen species. And cell experiment revealed that PC could decrease the expression of NFKB1 and TNF and increase the expression of FOXO3, SOD1, and GPX1 in H9C2 cells. These findings showed that the therapeutic mechanism of PC in the treatment of HF may be associated with the regulation of inflammation-related and oxidative stress-related genes.

Association of acylation-stimulating protein and receptor gene polymorphisms with coronary heart disease in Han and Hui populations.

OBJECTIVE: This study was to analyze the acylation-stimulating protein (ASP) (301T>C) and C5a-like receptor 2 (C5L2) (698C>T) gene polymorphisms in Han and Hui populations, and investigate their association with coronary heart disease (CHD). METHODS: 245 Han CHD patients and 110 Hui CHD patients from Shandong, Jinan, China were included in this study. Biochemical analysis was performed to assess the blood sugar and lipid levels in these patients, and the TaqMan genotyping assay was used to determine the genotype distribution. RESULTS: Our results showed that the C allele frequency in the ASP (301T>C) polymorphism in the Hui population was significantly higher than normal controls, while no significant differences were observed in the Han population, which might contribute to the genetic susceptibility of CHD in the Hui population. Moreover, for C5L2 (698C>T) gene polymorphism in both Han and Hui populations, the frequencies of the C/T genotype and T allele were significantly higher in the CHD patients compared with normal controls. Moreover, there were slight differences in the association of ASP and C5L2 gene polymorphisms with blood sugar and lipid levels between Han and Hui populations. CONCLUSIONS: Our results suggest differential ASP and C5L2 genotype distributions between Han and Hui patients, which might be associated with the different CHD-related genetic susceptibilities in these populations. These findings might contribute to a better understanding of the etiology and pathogenesis of CHD in different regions and populations.

Levels of acylation stimulating protein and the complement component 3 precursor are associated with the occurrence and development of coronary heart disease.

The aim of the present study was to investigate whether acylation stimulating protein (ASP) and complement component 3 (C3) are associated with the occurrence and development of coronary heart disease (CHD). The participants of the study were divided into three groups, including the healthy control (n=42), metabolic syndrome (MS, n=56) and CHD (n=62) groups. An enzyme-linked immunosorbent assay was used to measure the ASP concentrations, while an immunoturbidimetric assay was employed to determine the C3 concentrations. In addition, coronary angiography was performed to determine the severity of coronary artery disease in the CHD group. The CHD group was divided into three subgroups, according to the final Gensini score of coronary artery stenosis for each patient (mild, ≤20 points; moderate, 21-40 points; severe, >40 points). Western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed to analyze the protein and mRNA expression levels of C3 in the CHD subgroups and the healthy control group. The concentrations of ASP and C3 in the CHD group were found to be significantly higher compared with the control and MS groups. In addition, the levels of ASP and C3 in the mild and moderate CHD subgroups were significantly higher compared with the healthy controls or mild CHD patients. Furthermore, the protein expression levels of C3 in the moderate and severe CHD patients were found to be significantly higher compared with the healthy individuals and the mild CHD patients. The quantitative RT-PCR results revealed that the mRNA expression levels of C3 in the moderate and severe CHD patients were significantly higher compared with the healthy control group and the mild CHD patients. Furthermore, the mean levels of C3 transcripts in the severe CHD patients were found to be higher compared with the moderate CHD subgroup (P<0.05). Therefore, ASP and C3 were found to be associated with the occurrence and development of CHD; thus, may be used as novel indexes for CHD.