Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored. METHODS: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens. RESULTS: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues. CONCLUSIONS: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

Research on grading detection of the wheat seeds.

Evaluating the merits of the wheat seed is an important significance for wheat breeding. We studied analytic hierarchy process (AHP) for seeds grading by digital image processing techniques in the paper. Firstly, preprocess the collected wheat seed images; extract some parameters, such as area, plumpness, rectangular, and elongation of the seed, and then build the level model. Experiments showed the model is right, and level accuracy rate is more than 95%.

Development of a low glycemic maize starch: preparation and characterization.

A low glycemic index starch was developed by partial alpha-amylase treatment, and its fine structure responsible for slowly digestible and resistant properties was investigated. Different digestion rates were obtained for gelatinized, retrograded starch by varying the enzyme dosage and reaction time. Analysis by high performance size-exclusion chromatography (HPSEC) coupled with multiangle laser-light scattering indicated that the molecular weighs of amylopectin and amylose were reduced during the digestion, to less than 100 kDa. A debranched chain length study using high performance anion-exchange chromatography equipped with an amyloglucosidase reactor and a pulsed amperometric detector and HPSEC revealed that short chains of amylopectin and noncrystalline amylose were rapidly digested, while DPn 121 chains showed resistance, followed by DPn 46 chains. X-ray diffraction analysis revealed that the crystalline structure in the treated starches survived cooking. These starches not only have slowly digestible and resistant character, but also retain some branched structure for adequate functionality.