A comprehensive investigation of the medicinal efficacy of antimicrobial fusion peptides expressed in probiotic bacteria for the treatment of pan drug-resistant (PDR) infections.

The present work aimed to examine the intracellular antibacterial efficacy of Recombinant Lactobacillus acidophilus/antimicrobial peptides (AMPs) Melittin and Alyteserin-1a, specifically targeting Gram-negative bacteria. The first assessment was to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Recombinant L. acidophilus/AMPs versus Gram-negative and Gram-positive bacteria. In addition, the researchers examined the in vitro viability and safety of AMPs generated by L. acidophilus. The experiments included exposing the AMPs to elevated temperatures, proteases, cationic salts at physiological levels, and specific pH settings. The safety aspect was evaluated using hemolytic analysis utilizing sheep erythrocytes; cytotoxicity assays employing cell lines, and experiments on beneficial gut lactobacilli. An experiment was done using a time-kill method to assess the intracellular antibacterial efficacy of Recombinant L. acidophilus/AMPs compared to pathogenic varieties in HEp-2 cells. Previous investigations have shown that the MBC levels of recombinant L. acidophilus/AMPs were consistently two to four times higher than the equivalent MIC values when evaluated versus Gram-negative bacteria. Furthermore, the stability of the Recombinant L. acidophilus/AMPs showed variability when exposed to elevated temperatures (70 and 90 â„ƒ), treated with protease enzymes (proteinase K, lysozyme), exposed to higher concentrations of physiological salts (150 mM NaCl and 2 mM MgCl2), and varying pH levels (ranging from 4.0 to 9.0). The recombinant L. acidophilus/AMPs are non-hemolytic towards sheep erythrocytes, exhibit little cytotoxicity in RAW 264.7 and HEp-2 cells, and are considered safe when compared to beneficial gut lactobacilli. The research examined the intracellular bacteriostatic effects of recombinant L. acidophilus/AMPs on Gram-negative bacteria inside HEp-2 cells. Nevertheless, no notable bactericidal impact was seen on Gram-positive bacteria (P > 0.05). The research shows that recombinant L. acidophilus/AMPs, namely (L. acidophilus/melittin/Alyteserin-1a) as the focus of the investigation, effectively eliminate Gram-negative bacteria. Therefore, more investigation is necessary to elaborate on these discoveries.

Cancer stem cells: Recent trends in cancer therapy.

Cancer stem cells (CSCs) are a subset of tumor cells that were first identified in blood cancers (leukemia) and are considered promising therapeutic targets in cancer treatment. These cells are the cause of many malignancies including metastasis, heterogeneity, drug resistance, and tumor recurrence. They carry out these activities through multiple transcriptional programs and signaling pathways. This review summarizes the characteristics of cancer stem cells, explains their key signaling pathways and factors, and discusses targeted therapies for cancer stem cells. Investigating these mechanisms and signaling pathways responsible for treatment failure may help identify new therapeutic pathways in cancer.

Co-expression network analysis for the identification of potential prostate cancer genes and in vitro confirmation of their expression in cell model in the presence of Staphylococcal tsst-1 gene.

Prostate cancer has arisen as an important life-threatening malignancy in males worldwide. Therefore, it is important to study underlying molecular pathways to be able to proposed appropriate a novel pathway of apoptosis in prostate cancer. This study aimed to explore the molecular effects of Staphylococcal tsst-1 gene on PC3 cell line apoptosis by in silico and in vitro studies. In this work, the differential expression of genes in prostate cancer was predicted by analyzing the public dataset GSE132063. Then, the pcDNA3.1 (+) vector was used to transfer tsst-1 gene to the PC3 cells and its effects was investigated using flow cytometry and qPCR. Co-expression network analysis indicated that lncRNAs had strong relationship with apoptosis genes in prostate cancer. Results of protein-protein docking indicated that BCL2L11, GRAMD3 and EGR1 interacted with tsst-1. Finally, the flow cytometry results showed that transfection by pcDNA3.1 (+)- tsst-1 could increase cellular death rates (48.15%) compared with the pcDNA3.1 (+) groups (6.35%); and the expression levels of GRAMD3, EGR1, BCL2L11 and PLAC4 were dysregulated in tsst-1 -transfected PC3 compared with empty-transfected PC3 (p < .05). In conclusion, our data will provide a novel landscape to understanding the mechanism of Staphylococcal tsst-1 gene on the PC3 cells apoptosis pathways.

Integrative Analysis of lncRNAs in Kidney Cancer to Discover A New lncRNA (LINC00847) as A Therapeutic Target for Staphylococcal Enterotoxin tst Gene.

OBJECTIVE: Bacterial toxin can cause cell death through induction of apoptosis in cancer cell lines as well as changes in the expression patterns of long non-coding RNAs (lncRNAs) and genes. In the present study, the effect of tst gene on ACHN cell lines was reported along with proposing a novel pathway of apoptosis in kidney cancer. MATERIALS AND METHODS: In this experimental study, effective lncRNAs and genes were predicted from different criteria for renal cell carcinoma (RCC) by bioinformatics methods and lncRNA-miRNA-mRNA interaction was constructed; then the effect of Staphylococcus aureus tst gene on induction of apoptosis pathways on ACHN and HDF cell lines was investigated. RESULTS: After creation of lncRNA-miRNA-mRNA interaction, changes in expression levels of lncRNA LINC00847 (P=0.0024) and PTEN gene (P=0.0027) were identified, as potential apoptosis biomarkers for kidney cancer, after treating ACHN cell line by pCDNA3.1 (+)-tst compared to the empty vector. In contrast, there was no statistically significant difference in DICER1 expression levels in ACHN-tst cell (P≥0.05). In addition, transfection by pcDNA3.1 (+)-tst could increase ACHN cell apoptosis level (P<0.0001) compared to the pcDNA3.1 (+) group; but no significant effect was observed on normal cells. CONCLUSION: It is suggested that lncRNA LINC00847, discovered in this study, could provide a new landscape for researches aimed to determine relationship between functional lncRNA and RCC pathways. pcDNA3.1 (+)-tst was found to increase apoptosis in the transfected cells.