SALL4, a zinc-finger transcriptional factor for embryonic stem cell self-renewal and pluripotency, has been suggested to be involved in tumorigenesis. The role of SALL4 in human gastric cancer, however, remains largely unknown. In this study, we demonstrated that SALL4 was aberrantly expressed at both mRNA and protein levels in human gastric cancer tissues, and SALL4 level was highly correlated with lymph node metastasis. Enforced expression of SALL4 enhanced the proliferation and migration of human gastric cancer cells, whereas knockdown of SALL4 by siRNA led to the opposite effects. In addition, SALL4 overexpression promoted the growth and metastasis of gastric xenograft tumor in vivo. SALL4 overexpression induced epithelial-mesenchymal transition (EMT) in gastric cancer cells, with increased expression of Twist1, N-cadherin and decreased expression of E-cadherin. Moreover, SALL4 promoted the acquirement of stemness in gastric cancer cells through the induction of Bmi-1 and Lin28B. Taken together, our findings indicate that SALL4 has oncogenic roles in gastric cancer through the modulation of EMT and cell stemness, suggesting SALL4 as a novel target for human gastric cancer diagnosis and therapy.

Emerging evidence indicate that mesenchymal stem cells (MSCs) affect tumor progression by reshaping the tumor microenvironment. Neutrophils are essential component of the tumor microenvironment and are critically involved in cancer progression. Whether the phenotype and function of neutrophils is influenced by MSCs is not well understood. Herein, we investigated the interaction between neutrophils and gastric cancer-derived MSCs (GC-MSCs) and explored the biological role of this interaction. We found that GC-MSCs induced the chemotaxis of neutrophils and protected them from spontaneous apoptosis. Neutrophils were activated by the conditioned medium from GC-MSCs with increased expression of IL-8, TNFα, CCL2, and oncostatin M (OSM). GC-MSCs-primed neutrophils augmented the migration of gastric cancer cells in a cell contact-dependent manner but had minimal effect on gastric cancer cell proliferation. In addition, GC-MSCs-primed neutrophils prompted endothelial cells to form tube-like structure in vitro. We demonstrated that GC-MSCs stimulated the activation of STAT3 and ERK1/2 pathways in neutrophils, which was essential for the functions of activated neutrophils. We further revealed that GC-MSCs-derived IL-6 was responsible for the protection and activation of neutrophils. In turn, GC-MSCs-primed neutrophils induced the differentiation of normal MSCs into cancer-associated fibroblasts (CAFs). Collectively, our results suggest that GC-MSCs regulate the chemotaxis, survival, activation, and function of neutrophils in gastric cancer via an IL-6–STAT3–ERK1/2 signaling cascade. The reciprocal interaction between GC-MSCs and neutrophils presents a novel mechanism for the role of MSCs in remodeling cancer niche and provides a potential target for gastric cancer therapy.

The mycotoxin ochratoxin A (OTA) is a common contaminant of various plant-derived foods and feeds. However, methods for complete decontamination remain to be established. Recently, biological approaches for mycotoxin removal using various species of yeast have been explored. In the present study, we investigated the efficacy of OTA degradation by the yeast Yarrowia lipolytica under various conditions, altering yeast concentration, temperature, pH, and concentration of OTA in order to determine the optimal requirements of this species. At a yeast concentration of 108 cells/ml, the degradation rate was higher than that observed at any other concentration and, after 24 h, the OTA concentration was reduced to almost half of the initial level introduced to the culture. Further, Y. lipolytica cultured at 28 °C showed the highest level of OTA degradation. Similarly, the culture performed optimally at a pH of 4. The initial concentration of OTA also affected the ability of the yeast to degrade OTA, with the level of degradation being the highest when the initial OTA concentration was 0.1 μg/ml. Moreover, we also tested the toxicity of the OTA biodegradation products using HepG2 cells to determine the physiological applicability of this yeast species in the food industry and observed that these products were notably less toxic than non-degraded OTA. Y. lipolytica effectively reduced natural decay incidence of grapes, and had no negative effect to the storage quality of grape fruits. Taken together, these data suggest that Y. lipolytica could be a viable OTA contamination prevention/treatment option and additional research concerning its commercial use is warranted.

Inhibition of angiotensin I‐converting enzyme (ACE) activity is effective in reducing blood pressure. Wheat germ protein, an important by‐product of the flour milling industry, is rich in ACE inhibitory peptides. In this article, wheat germ protein was pretreated with ultrasound ranging from 200 to 1800 W before hydrolysis, and response surface methodology (RSM) was employed to optimize enzymatic hydrolysis conditions for the preparation of ACE inhibitory peptides. The results showed that ultrasonic pretreatment increased the ACE inhibitory activity of the peptides released from wheat germ protein. When wheat germ protein was pretreated with ultrasound at 600 W for 10 min, the ACE inhibitory activity was increased by 32.14% over the control. Single‐factor experiments displayed that the change in ACE inhibitory activity was not consistent with the degree of hydrolysis (DH). For the pretreated protein, the optimum RSM operating conditions were: hydrolysis time of 88.14 min, substrate concentration of 1.17% and enzyme to substrate (E/S) ratio of 2.18%. Under this condition, ACE inhibitory activity of the hydrolysate was 68.96%, being closely associated with the predicted value (69.68%) from the model generated based on RSM optimization. Practical Applications Food protein‐based antihypertensive peptides are welcomed by patients for the advantages of being safer, easily absorbed, and stable without side effects. Wheat germ protein is an abundant and low‐cost by‐product of the flour milling industry, which is a potential protein resource for preparation of ACE inhibitory peptides. In this article, combination of ultrasound pretreatment and enzymatic hydrolysis was confirmed to be an effective way for preparation of ACE inhibitory peptides from wheat germ protein. Besides, parameters of the preparation process were optimized, providing a good reference for industrial production of ACE inhibitory peptides.

Biological control of mycotoxin in cereals, fruits and vegetables have emerged as a promising method. In a previous study, Yarrowia lipolytica Y-2 isolated by our research team showed biocontrol effect on the post-harvest decay of grapes and ochratoxin A (OTA) elimination in polytoma medium. The aim of this study was to elucidate the possible mechanisms of OTA elimination by Y. lipolytica Y-2. The results indicated that OTA elimination by Y. lipolytica Y-2 was attributed to the degradation action of intracellular enzymes but not extracellular enzymes. A degradation product was identified as ochratoxin alpha (OT ) by liquid chromatography-tandem mass spectrometry. The intracellular enzymes precipitated with 65% saturation of ammonium sulphate degrade OTA the most quickly and 97.2% OTA was degraded within 4 h. Analysis of this fraction showed that two proteins of carboxypeptidase were expressed in Y. lipolytica Y-2 but not in Y. lipolytica Polh without the ability to degrade OTA. The results of the protein identification combined with product identification indicated that OTA was degraded to OT by Y. lipolytica Y-2 through the hydrolysis activity of carboxypeptidases. Additionally, many proteins of Y. lipolytica Y-2 involved in stress response and reactive O 2 species elimination also played essential role in OTA degradation.