Background: Zinc oxide nanoparticles (ZnO NPs) are known as one of the important inorganic materials used in research and health-related applications with effective antibacterial activities. Although the toxic effects of ZnO NPs have already been evaluated, more information is required to understand the possible mechanisms. Objectives: The aim of the present study was to determine the influences of pH and temperature on antibacterial activity of ZnO NPs against some strains of pathogenic bacteria. Identifying the interrelationship between toxicity and cultural conditions helps us to have a better understanding of the optimum reaction conditions for maximum antimicrobial activity. Materials and Methods: ZnO NPs were prepared and characterized and then dispersed in glycerol with the help of ammonium citrate as the dispersant. The antibacterial tests were performed by measuring the growth of Escherichia coli O157:H7 and Staphylococcus aureus with different concentrations of ZnO NPs in glycerol. All the experiments were conducted at different incubation temperatures (25-42^°C) and pH levels (4-10 for E. coli O157:H7 and 5-10 for S. aureus). Results: The results showed that ZnO nanofluid have antibacterial activity against E. coli O157:H7 and S. aureus and the inhibitory effect increases with increasing the nanofluid concentration. The experiments showed that the antibacterial activity of ZnO NPs was influenced by temperature and pH. Higher antibacterial activity was observed at acidic pH levels with the maximum toxicity at pH = 4 and pH = 5 for E. coli O157: H7 and S. aureus, respectively. By raising the temperature, the toxicity of ZnO nanofluid increased, with the highest antibacterial activity at 42°C for both bacterial types in comparison with positive controls under the same conditions. Conclusions: Analysis of the results demonstrated that exposure media of ZnO NPs and cultural factors play a role in their cytotoxic effects. It could be attributed to the principal mechanism at different reaction conditions. Keywords: Escherichia coli O157: H7; Treatment; Staphylococcus aureus; Nanoparticles

Acquired resistance to oxaliplatin is considered as the primary reason for failure in colorectal cancer (CRC) therapy. Identifying the underlying resistance mechanisms may improve CRC treatment. The present study aims to identify the key genes involved in acquired oxaliplatin-resistant in CRC by confirming the oxaliplatin resistance index (OX-RI). To this aim, two public microarray datasets regarding oxaliplatin-resistant CRC cells with different OX-RI, GSE42387, and GSE76092 were downloaded from GEO database to identify differentially expressed genes (DEGs). The results indicated that the OX-RI affects the gene expression pattern significantly. Then, 54 common DEGs in both datasets including 18 up- and 36 down-regulated genes were identified. Protein-protein interaction (PPI) analysis revealed 13 up- (MAGEA6,TGM2,MAGEA4,SCHIP1,ECI2,CD33,AKAP12,MAGEA12,CALD1,WFDC2,VSNL1,HMGA2, andMAGEA2B) and 12 down-regulated (PDZK1IP1,FXYD3,ALDH2,CEACAM6,QPRT,GRB10,TM4SF4,LGALS4,ALDH3A1,USH1C,KCNE3, andCA12) hub genes. In the next step, two novel up-regulated hub genes includingECI2andSCHIP1were identified to be related to oxaliplatin resistance. Functional enrichment and pathway analysis indicated that metabolic pathways, proliferation, and epithelial-mesenchymal transition may play dominant roles in CRC progression and oxaliplatin resistance. In the next procedure, two in vitro oxaliplatin-resistant sub-lines including HCT116/OX-R4.3 and HCT116/OX-R10 cells with OX-IR 3.93 and 10.06 were established, respectively. The results indicated the up-regulation ofTGM2andHMGA2in HCT116/OX-R10 cells with high OX-RI and down-regulation ofFXYD3,LGALS4, andECI2in both cell types. Based on the results,TGM2,HMGA2,FXYD3, andLGALS4genes are related to oxaliplatin-resistant CRC and may serve as novel therapeutic targets.

Background and Objectives: Arginine-rich peptides are an important class of antimicrobial peptides (AMPs) that exert their antibacterial activity via a lytic mechanism. Although the antibacterial activity of arginine-rich peptides has been already evaluated, no reports have so far been evaluated the influence of reaction conditions on their antimicrobial potential. The aim of the present study was to investigate the influence of pH, temperature, and glycine on antibacterial activity of poly-l-arginine (PLA) with a molecular weight of 5-15 kDa against Escherichia coli O157:H7 and Staphylococcus aureus. Materials and Methods: The percentage of growth inhibition of PLA against both bacteria was analyzed at various pH, temperatures and sub-inhibitory concentrations of glycine by two-fold broth microdilution method. Results: The results showed that PLA had antibacterial activity against E. coli O157:H7 and S. aureus and the inhibitory effect increased with increasing PLA concentration. The antimicrobial activity of PLA against both microorganisms was higher in basic media than under acidic or neutral conditions. At 1/2 times the MIC, heat treatment intensified the toxicity of PLA against E. coli O157:H7 whereas the susceptibility to PLA seems to be temperature independent for S. aureus. The MICS of glycine against E. coli O157:H7 and S. aureus were 12.5 and 25 mg ml(-1), respectively. The antibacterial activity of PLA against both microorganisms increased, as indicated by the increasing growth inhibition percentage of this peptide with increasing glycine concentration. Conclusion: The antibacterial activity of PLA against S. aureus and E. coli O157:H7 depends on pH and glycine concentration.

KRAS mutation is responsible for 40–50% of colorectal cancers (CRCs). RNA-seq data and bioinformatics methods were used to analyze the transcriptional profiles of KRAS mutant (mtKRAS) in comparison with the wild-type (wtKRAS) cell lines, followed by in-silico and quantitative real-time PCR (qPCR) validations. Gene set enrichment analysis showed overrepresentation of KRAS signaling as an oncogenic signature in mtKRAS. Gene ontology and pathway analyses on 600 differentially-expressed genes (DEGs) indicated their major involvement in the cancer-associated signal transduction pathways. Significant hub genes were identified through analyzing PPI network, with the highest node degree for PTPRC. The evaluation of the interaction between co-expressed DEGs and lncRNAs revealed 12 differentially-expressed lncRNAs which potentially regulate the genes majorly enriched in Rap1 and RAS signaling pathways. The results of the qPCR showed the overexpression of PPARG and PTGS2, and downregulation of PTPRC in mtKRAS cells compared to the wtKRAS one, which confirming the outputs of RNA-seq analysis. Further, significant upregualtion of miR-23b was observed in wtKRAS cells. The comparison between the expression level of hub genes and TFs with expression data of CRC tissue samples deposited in TCGA databank confirmed them as distinct biomarkers for the discrimination of normal and tumor patient samples. Survival analysis revealed the significant prognostic value for some of the hub genes, TFs, and lncRNAs. The results of the present study can extend the vision on the molecular mechanisms involved in KRAS-driven CRC pathogenesis.