Elaeagnus angustifolia Plant Extract Inhibits Angiogenesis and Downgrades Cell Invasion of Human Oral Cancer Cells via Erk1/Erk2 Inactivation.

Oral cancer is a common malignancy in both men and women worldwide; this cancer is characterized by a marked propensity for invasion and spreading to local lymph nodes. On the other hand, Elaeagnus angustifolia (EA) is a medicinal plant that has been used for centuries for treating many human diseases in the Middle East. However, the effect of EA plant extract on human cancers especially oral has not been investigated yet. Thus, first we examined the outcome of EA flower extract on angiogenesis, using the chorioallantoic membrane (CAM) of the chicken embryo; we found that EA extract reduces blood vessel development of the CAM. Then, we investigated the effect of EA flower extract on selected parameters in FaDu and SCC25 oral cancer cell lines. Our results show that EA extract inhibits cell proliferation and colony formation, in addition to the initiation of S cell cycle arrest and reduction of G1/G2 phase. In parallel, EA extract provokes differentiation to an epithelial phenotype "mesenchymal-to-epithelial transition: MET" which is the opposite of "epithelial-to-mesenchymal transition, EMT": an important event in cell invasion and metastasis. Thus, EA plant extract causes a dramatic decrease in cell invasion and motility abilities of FaDu and SCC25 cancer cells in comparison with their controls. These changes are accompanied by an upregulation of E-cadherin expression. The molecular pathway analysis of the EA flower extract reveals that it can inhibit the phosphorylation of Erk1/Erk2, which could be behind the inhibition of angiogenesis, the initiation of MET event, and the overexpression of E-cadherin. Our findings indicate that EA plant extract can reduce human oral cancer progression by the inhibition of angiogenesis and cell invasion via Erk1/Erk2 signaling pathways.

In silico Designing of an Epitope-Based Vaccine Against Common E. coli Pathotypes.

Escherichia coli (E. coli) is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While E. coli can stay as an innocuous resident in the digestive tract, it can cause a group of symptoms ranging from diarrhea to live threatening complications. Due to the increased rate of antibiotic resistance worldwide, the development of an effective vaccine against E. coli pathotypes is a major health priority. In this study, a reverse vaccinology approach along with immunoinformatics has been applied for the detection of potential antigens to develop an effective vaccine. Based on our screening of 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane protein assembly factor (BamA) as vaccine candidates for the current study. The conservancy of these proteins in the main E. coli pathotypes was assessed through BLASTp to make sure that the designed vaccine will be protective against major E. coli pathotypes. The multitope vaccine was constructed using cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes with suitable linkers and adjuvant. Following that, it was analyzed computationally where it was found to be antigenic, soluble, stable, and non-allergen. Additionally, the adopted docking study, as well as all-atom molecular dynamics simulation, illustrated the promising predicted affinity and free binding energy of this constructed vaccine against the human Toll-like receptor-4 (hTLR-4) dimeric state. In this regard, wet lab studies are required to prove the efficacy of the potential vaccine construct that demonstrated promising results through computational validation.