Platelet granule secretion plays a key role in atherothrombosis. Curcumin, a natural polyphenol compound derived from turmeric, exerts multiple biological activities. The current study sought to investigate the efficacy of tetrahydrocurcumin (THC, the major active metabolite of curcumin) on platelet granule secretion in vitro and thrombus formation in vivo. We found that THC significantly attenuated agonist-induced granule secretion in human gel-filtered platelets in vitro, including CD62P and CD63 expression and platelet factor 4, CCL5, and adenosine triphosphate release. These inhibitory effects of THC were partially mediated by the attenuation of cytosolic phospholipase A2 (cPLA2) phosphorylation, leading to a decrease in thromboxane A2 (TxA2) generation. Moreover, the MAPK (Erk1/2, JNK1/2, and p38 MAPK) signaling pathways were downregulated by THC treatment, resulting in reduced cPLA2 activation, TxA2 generation, and granule secretion. Additionally, THC and curcumin attenuated murine thrombus growth in a FeCl3-induced mesenteric arteriole thrombosis model in C57BL/6J mice without prolonging the tail bleeding time. THC exerted more potent inhibitory effects on thrombosis formation than curcumin. Through blocking cyclooxygenase-1 activity and thus inhibiting platelet TxA2 synthesis and granule secretion with aspirin, we found that THC did not further decrease the inhibitory effects of aspirin on thrombosis formation. Thus, through inhibiting MAPKs/cPLA2 signaling, and attenuating platelet TxA2 generation, granule secretion, and thrombus formation, THC may be a potent cardioprotective agent.
The contamination of semi-volatile organic compounds (SVOCs) in the surface sediments of the Guan River Estuary, China was fully investigated. Total concentrations of 56 species of SVOCs ranged from 132 to 274 ng/g with an average of 186 ng/g (dry weight). Polycyclic aromatic hydrocarbon (PAH) concentrations were positively correlated with clay content and negatively correlated with sediment grain size. Source identification indicated that PAHs originated mainly from pyrolytic sources. However, intense ship traffic in the estuary may provide sources of petrogenic PAHs. Organochlorine pesticides (OCPs) mainly originated from direct input of dichlorodiphenyltrichloroethanes (DDTs) during some industrial processes. The SVOC concentrations were also compared with International Sediments Quality Guidelines and Sediments Quality Criteria, and the results indicated that negative biological impacts may originate from high concentrations of FLO, p,p'-DDE, and total DDTs.
Background:The objective of the present study was to predict candidate genes with prognostic information for lung adenocarcinoma (LUAD). Methods: Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network of deferentially expressed genes (DEGs) in GSE32863. Key genes were identified as the intersecting genes of the modules of WGCNA and DEGs. Kaplan-Meier plotter was employed to conduct survival analysis. Enrichment analysis was performed. The expression of key genes in LUAD was validated. Then, we performed in vitro experiments to explore functions of key genes. We overexpressed DYNLRB2 in A549 cell. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were test expression levels and functional analyses were performed, including cell viability, apoptosis. Results: A total of 1,587 DEGs in GSE32863 were identified, including 649 up-regulated genes and 938 down-regulated genes. In coexpression analysis, there were 1,271 hubgenes from the modules that were chosen for further analysis. 15 key genes were identified as the intersecting genes of the modules of WGCNA and DEGs. The expressions of dynein light chain roadblock-type 2 (DYNLRB2) and mouse homolog of ß1 spectrin (SPTBN1) were lower in LUAD, and were associated with survival time of LUAD patients. GSEA results showed that high expressed DYNLRB2 and SPTBN1 were enriched in Drug metabolism cytochrome P450, Cardiac muscle contraction, Retinol metabolism. Down-regulated DYNLRB2 and SPTBN1 were associated with Homologous recombination, Progesterone mediated oocyte maturation, Base excision repair. The in vitro experiment confirmed the overexpression of DYNLRB2 in A549 transferred cells. The overexpress DYNLRB2 inhibited cell viability and induced apoptosis.Conclusions: Our study suggested that DYNLRB2 and SPTBN1 might be potential tumor suppressor genes and could serve as biomarkers for predicting the prognosis of LUAD patients.
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