Synergistic effect of lecithin and alginate, CMC, or PVP in stabilizing curcumin and its potential mechanism.

This work aims to advance the understanding of the synergistic mechanism of lecithin and polymers (alginate, CMC, and PVP) in stabilizing curcumin, with a major focus on understanding the nanocomplex formation process and the main binding energy between molecules. It is demonstrated that lecithin and polymers have a synergistic effect in increasing the thermal acid, light, and digestion stability of curcumin. The potential mechanism is that the hydrophobic parts of curcumin molecules are first anchored at the region of the hydrophobic cavity of lecithin by van der Waals, while the hydrophilic parts are outward and are further encapsulated by hydrophilic polymers by van der Waals and electrostatic interaction to form a protective shell. This study contributes to our understanding of the synergistic mechanism of lecithin, polymers, and hydrophobic compounds, which can promote the synergistic use of lecithin and polymers to prepare nanocomplexes as an important tool for delivering bioactive compounds.

HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4.

PURPOSE: Chemoresistance remains a major challenge in the therapy of gastric cancer (GC). The homeobox (HOX) gene family has gained attention in carcinogenesis and chemoresistance. Here, this study aimed to explore the mechanism of HOXA13 in GC chemoresistance. METHODS: Quantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate the expression of HOXA13 in GC tissues. The Kaplan-Meier plotter database was mined for prognosis analysis of GC patients with different HOXA13 expression receiving 5-Fluorouracil (5-FU) therapy. The effects of HOXA13 on sensitivity of GC cells to 5-FU were investigated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) incorporation, flow cytometry and experiment in vivo. RNA-Sequencing analysis was performed to explore the underlying mechanism of HOXA13-mediated 5-FU resistance in GC. Chromatin immunoprecipitation (ChIP) and rescue experiments were applied to determine the relationship between HOXA13 and ABCC4. Luciferase reporter assay was performed to assess interaction of miR-139-5p and HOXA13. RESULTS: HOXA13 was upregulated in GC and its high expression was associated with poor prognosis of GC patients with 5-FU treatment. Overexpression of HOXA13 impaired the inhibitory effects of 5-FU on GC cells proliferation in vitro and vivo, and knockdown of HOXA13 exacerbated 5-FU-induced GC cells apoptosis. Mechanistically, HOXA13, directly targeted by miR-139-5p in GC, might upregulate ABCC4 expression, thereby accentuating 5-FU resistance of GC cells. CONCLUSION: Our study suggests that HOXA13 attenuates 5-FU sensitivity of GC possibly by upregulating ABCC4. Thus, targeting HOXA13 would provide a novel prospective into the potential therapeutic strategy for reversing chemoresistance.

TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway.

Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells in vitro and in vivo. Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell via activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC.