Background: Nasopharyngeal carcinoma tends to present at an advanced stage because the primary anatomic site is located in a less visible area and its clinical symptoms are nonspecific. Prognosis of advanced nasopharyngeal carcinoma cases remains disappointing. SEPT9 is a methylation-based biomarker approved by the US Food and Drug Administration for colorectal cancer screening and diagnosis. Interestingly, downregulation of SEPT9, especially SEPT9_v2, mediated by promoter hypermethylation has been also detected in head and neck squamous cell carcinoma than in head and neck squamous epithelium, while other SEPT9 variants did not. These reasons above indicate a crucial role of SEPT9_v2 in cancer progression. Therefore, we address the methylation status of SEPT9_v2 in nasopharyngeal carcinoma and explore the role of SEPT9_v2 in nasopharyngeal carcinoma proliferation and cancer progression. Results: SEPT9_v2 expression was found to be downregulated via promoter methylation in nasopharyngeal carcinoma cell lines and tissues. Ectopic expression of SEPT9_v2 induced G0/G1 cell cycle arrest and apoptosis, which exerted an inhibitory effect in cell proliferation and colony formation. Additionally, nasopharyngeal carcinoma cell migration and invasion were shown to be inhibited by SEPT9_v2. Furthermore, our data suggested that SEPT9_v2 inhibits proliferation and migration of nasopharyngeal carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10. Conclusions: This study delineates SEPT9_v2, frequently silenced by promoter hypermethylation, exerts anti-tumor functions through inactivation of the Wnt/β-catenin signaling pathway via miR92b-3p/FZD10 in nasopharyngeal carcinoma cells and, hence, SEPT9_v2 may be a promising therapeutic target and biomarker for nasopharyngeal carcinoma.
Mesangioproliferative glomerulonephritis (MsPGN) is a common human kidney disease. Rat Thy-1 nephritis (Thy-1N) is an animal model widely used for the study of MsPGN. Thy-1N is not only sublytic C5b-9-dependent, but also related to pro-inflammatory cytokine production and macrophage (Mφ) accumulation in rat renal tissues. In this study, we found that the expression or phosphorylation of chemokine CCL3/4, CD68 (Mφ marker), IRF-8, PKC-α and NF-κB-p65 (p65) were all up-regulated both in the renal tissues of Thy-1N rats (
in vivo
) and in the glomerular mesangial cells (GMCs) upon sublytic C5b-9 stimulation (
in vitro
). Further experiments
in vitro
revealed that the phosphorylated PKC-α (p-PKC-α) could promote p65 phosphorylation, and then p-p65 enhanced IRF-8 expression through binding to IRF-8 promotor (-591 ~ -582 nt and -299 ~ -290 nt). Additionally, up-regulation or silencing of IRF-8 gene promoted or reduced CCL3/4 production, and then regulated Mφ chemotaxis. The underlying mechanism involved in IRF-8 binding to CCL3 promoter (-249 ~ -236 nt), which resulted in CCL3 gene transcription. The experiments
in vivo
showed that knockdown of renal PKC-α, p65, IRF-8 and CCL3/4 genes could inhibit CCL3/4 production, Mφ accumulation, GMC proliferation and proteinuria of Thy-1N rats. Furthermore, p-PKC-α, p-p65, IRF-8, CCL3/4 expression and Mφ accumulation were also increased in the renal tissues of MsPGN patients. Collectively, these findings indicate that sublytic C5b-9 induces CCL3/4 production and Mφ accumulation via PKC-α/p65/IRF-8 axis, and finally aggravates the pathological changes of MsPGN.
In this work, a dense and acid-resistant beta zeolite membrane was applied to improve the esterification of citric acid and n-butanol, for the first time. Through the continuous removal of the by-product water via pervaporation (PV), the conversion of citric acid was significantly enhanced from 71.7% to 99.2% using p-Toluenesulfonic acid (PTSA) as catalyst. PTSA was a well-known strong acid, and the membrane kept almost no change after PV-esterification, indicating the superior acid resistance of beta zeolite membrane. Compared to the use of acid-resistant MOR zeolite membrane by PV-esterification, a consistently higher conversion of citric acid was obtained using a high-flux beta zeolite membrane. The results showed that high water permeation on the beta zeolite membrane, with good acid resistance, had a strong promoting effect on esterification, leading to an improved conversion. In addition, the citric acid conversion of 97.7% could still be achieved by PV-esterification at a low reaction temperature of 388 K.
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