Galangin Enhances Anticancer Efficacy of 5-Fluorouracil in Esophageal Cancer Cells and Xenografts Through NLR Family Pyrin Domain Containing 3 (NLRP3) Downregulation.

BACKGROUND Galangin is believed to exert antioxidant effects by inhibition of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, which has been linked to chemotherapy sensitivity in cancers. In this study, we explored the synergistic effect of galangin in combination with the chemotherapy agent 5-fluorouracil (5-FU) in esophageal cancer cells and xenografts. MATERIAL AND METHODS The esophageal squamous epithelium cell line Het-1A and 2 human esophageal cancer cell lines (Eca109, OE19) were used to investigate the effect of galangin with or without 5-FU in vitro through proliferation and invasion analyses, while apoptosis was analyzed in cancer cells. Furthermore, a subcutaneous xenograft tumor model in mice was used to study cancer development in vivo. RESULTS Compared with 5-FU monotherapy, combined galangin and 5-FU treatment reduced human esophageal cancer cell growth activities and invasion abilities. The results suggested that galangin had a chemotherapy-sensitized synergistic antitumor effect induced by 5-FU. The susceptibility of cancer cells to apoptosis, which is linked with chemotherapy sensitivity, was induced by 5-FU and further enhanced by galangin. NLRP3 was identified as being significantly activated by 5-FU, but galangin treatment reversed the effect and inhibited NLRP3 expression, which was accompanied by downregulated interleukin-1b levels. Further investigation showed that the induced apoptotic cascade can be mostly reversed by incubation with an NLRP3 activator, irrespective of AKT signaling. Using xenograft mouse models, we found that galangin exposure further restrained cancer development after 5-FU treatment and increased sensitivity to chemotherapy by suppressing the NLRP3 inflammasome pathway. CONCLUSIONS Our results indicated that galangin played a synergistic anticancer role through NLRP3 inflammasome inhibition when paired with FU-5.

Effect of Lactobacillus fermentum TKSN041 on improving streptozotocin-induced type 2 diabetes in rats.

With the increasing incidence of type 2 diabetes, it is imperative to identify how to effectively prevent or treat this disease. Studies have shown that some lactic acid bacteria can improve type 2 diabetes with almost no side effects. Therefore, in this experimental study, we explored the preventive and therapeutic effects of Lactobacillus fermentum TKSN041 (L. fermentum TKSN041) on streptozotocin-induced type 2 diabetes in rats. The results showed that L. fermentum TKSN041 could reduce the amount of water intake, reduce weight loss, and control the increase in the fasting blood glucose level of diabetic rats. The organ index and tissue section results showed that L. fermentum TKSN041 could reduce the damage caused by diabetes to the liver, kidney, spleen, pancreatic, and brain tissue. Furthermore, L. fermentum TKSN041 decreased the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), aminotransferase (AST), alanine aminotransferase (ALT), glycated serum proteins (GSP), malondialdehyde (MDA), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and endothelin 1 (ET-1) in serum and increased the serum levels of high-density lipoprotein cholesterol (HDL) and interleukin 10 (IL-10). Finally, L. fermentum TKSN041 up-regulated the mRNA and protein expressions of NF-kappa-B inhibitor-α (IκB-α), AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), liver kinase B1 (LKB1), and glucose transporter 4 (GLUT4) and down-regulated those of nuclear factor-κBp65 (NFκB-p65) and tumor necrosis factor alpha (TNF-α). Furthermore, LF-TKSN041 up-regulated the mRNA expressions of peroxisome proliferator-activated receptor γ (PPAR-γ) and down-regulated neuropeptide Y (NPY), sterol regulatory element-binding protein-1 (SREBF-1), and vascular endothelial growth factor (VEGF). These results suggest that L. fermentum TKSN041 may be a useful intervention factor for the prevention or treatment of type 2 diabetes induced by STZ. Clinical trials are needed to further demonstrate its effectiveness.

IL-6 and TNF-α promote metastasis of lung cancer by inducing epithelial-mesenchymal transition.

The characteristics of cancer cells, such as invasiveness, are affected by the tumor microenvironment. Studies have shown that interleukin (IL)-6 and tumor necrosis factor (TNF)-α regulate the proliferation of lung cancer. However, few studies have focused on the effects of IL-6 and TNF-α on metastasis of lung cancer. The present study was designed to investigate whether IL-6 and TNF-α can promote metastasis of non-small cell lung cancer (NSCLC). Sixty-five tumor and matched adjacent tissue samples from patients with NSCLC and corresponding serum samples were collected. Thirty serum samples from healthy subjects were selected as controls. Real-time PCR and western blot analysis were used to measure IL-6, TNF-α, vimentin, E-cadherin, and N-cadherin expression in tissue samples; ELISA was used to measure IL-6 and TNF-α expression in serum samples. The correlation of serum levels of IL-6 and TNF-α with the clinical stage was analyzed; the correlation of IL-6 and TNF-α levels in serum with these tissues was analyzed; the correlation of serum levels of IL-6 and TNF-α with lymph node metastasis and distant metastasis was analyzed. Expression of IL-6 and TNF-α were significantly increased compared with controls in both serum and tissue; IL-6 and TNF-α levels were positively correlated with lymph node metastasis and distant metastasis; IL-6 and TNF-α levels were negatively correlated with E-cadherin level and were positively correlated with N-cadherin and vimentin levels. In conclusion, IL-6 and TNF-α can induce epithelial-mesenchymal transition, and subsequently promote metastasis of lung cancer. Anti-inflammation should be considered for the treatment of lung cancer.

[Surface modification of RGD peptides onto acellularized porcine aortic valve to promote cell adhesion].

OBJECTIVE: To investigate the impact of RGD peptides on cell adhesion to acellularized procine aortic valve. METHODS: The acellular porcine aorta valve (APAV) was prepared by removing the cells and cellular components from porcine aortic valve using trypsin and hyposmosis TritonX-100. With the help of epoxy chloropropane (EC), the decelluarized valve scaffolds were immobilized with YGRGDSP peptide. MFBs were seeded onto four groups [acellularized value (AV) group, EC group, glutaraldehyde+EC (GE) group and EC+ RGD group or GE+RGD group] of coupled, coated and untreated decelluarized valve scaffolds. Ninhydrin reaction, cell count and fluorescent imaging test were employed to examine the efficiency of cell adhesion. RESULTS: More cells were attached to the decellularized valve scaffolds when the cells were coupled with RGD peptides compared with the others. The adhesive effect was correlated with the concentration of the RGD peptide and the attaching time. CONCLUSION: With the help of EC, YGRGDSP peptides can be immobilized by covalent bonding. RGD peptides improve cell adhesion to decellularized valve scaffolds.