Evaluation on the effect of hydrogen sulfide on the NLRP3 signaling pathway and its involvement in the pathogenesis of atherosclerosis.

BACKGROUND: As a common disease, the incidence of atherosclerosis (AS) in the world is high. Therefore, we aimed to evaluate the involvement of hydrogen sulfide (H 2 S)/cystathionine γ-lyase (CSE) in the pathogenesis of AS as well as their possible signaling pathways. METHODS: Enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis were used to detect the effect of CSE on the expression of inflammatory cytokines, ie, H 2 S, thioredoxin-interacting protein (TXNIP), NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, and interleukin (IL)-1ß. In addition, immunohistochemistry and Western blot analysis were performed to detect the levels of TXNIP, NLRP3, ASC, caspase-1, IL-1ß, and IL-18 among different groups. RESULT: Knockdown of CSE by the transfection of CSE small interfering RNA upregulated the levels of two inflammatory cytokines, ie, IL-1ß and IL-18. In addition, the downregulation of CSE promoted the expression of TXNIP, NLRP3, ASC, caspase-1, and IL-1ß in THP-1 cells. Meanwhile, treating the cells with sodium hydrosulfide (NaHS) inhibited the productions of IL-1ß and IL-18. Furthermore, upregulation of H 2 S synthesis by treating the cells with NaHS also reduced the protein levels of TXNIP, NLRP3, ASC, caspase-1, and IL-1ß. Finally, the protein levels of TXNIP and NLRP3 in the AS group were much higher than those in the AS + H 2 S group, which in turn was higher than the sham group. In addition, the AS group displayed the highest protein levels of TXNIP, NLRP3, ASC, caspase-1, IL-1ß, and IL-18, while the levels of these proteins in the AS + H 2 S group were higher than those in the sham group. CONCLUSION: In summary, the present finding suggested a possible linkage between H 2 S metabolism and AS through the H 2 S/CSE-TXNIP-NLRP3-IL-18/IL-1ß-nitric oxide (NO) signaling pathway.

A long noncoding RNA MAP3K1-2 promotes proliferation and invasion in gastric cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been implicated in several human cancers. The expression profile and underlying mechanism of the lncRNA MAP3K1-2 in gastric cancer (GC) are poorly understood. METHODS: Sixty-one patients with GC were recruited from Shanghai Baoshan Luo Dian Hospital (Shanghai, China). Tumor tissues and paired normal tissues (5 cm adjacent to the tumor) were obtained. Expression of lncRNA MAP3K1-2 in GC cell lines was examined using quantitative real-time polymerase chain reaction. Protein expression was detected using Western blot. Cell cycle analysis was assessed using flow cytometry. Cell proliferation was assessed using soft agar assays, and cell invasion was assessed using Transwell assays. RESULTS: The expression level of lncRNA MAP3K1-2 was upregulated in GC cells and markedly higher in poorly differentiated cell lines. Silencing treatment of lncRNA MAP3K1-2 significantly inhibited cell proliferation and invasion in GC. In addition, knockdown of lncRNA MAP3K1-2 significantly inhibited the function of important genes in the MAPK signaling pathway. Higher expression of lncRNA MAP3K1-2 was often associated with poorer prognosis in patients with GC. CONCLUSIONS: lncRNA MAP3K1-2 is a critical effector in GC tumorigenesis and progression, representing novel therapeutic targets. High lncRNA MAP3K1-2 expression may serve as a novel independent prognostic marker for predicting the outcome of GC.