Probiotic-derived silver nanoparticles target mTOR/MMP-9/BCL-2/dependent AMPK activation for hepatic cancer treatment.

Recent advances in nanotechnology have offered novel ways to combat cancer. By utilizing the reducing capabilities of Lactobacillus acidophilus, silver nanoparticles (AgNPs) are synthesized. The anti-cancer properties of AgNPs have been demonstrated in previous studies against several cancer cell lines; it has been hypothesized that these compounds might inhibit AMPK/mTOR signalling and BCL-2 expression. Consequently, the current research used both in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs could inhibit cell proliferation autophagy and promote apoptosis in HepG2 cells. The isolated strain was identified as Lactobacillus acidophilus strain RBIM based on 16 s rRNA gene analysis. Based on our research findings, it has been observed that this particular strain can generate increased quantities of AgNPs when subjected to optimal growing conditions. The presence of silanols, carboxylates, phosphonates, and siloxanes on the surface of AgNPs was confirmed using FTIR analysis. AgNPs were configured using UV-visible spectroscopy at 425 nm. In contrast, it was observed that apoptotic cells exhibited orange-coloured bodies due to cellular shrinkage and blebbing initiated by AgNP treatment, compared to non-apoptotic cells. It is worth mentioning that AgNPs exhibited remarkable selectivity in inducing cell death, specifically in HepG2 cells, unlike normal WI-38 cells. The half-maximum inhibitory concentration (IC50) values for HepG2 and WI-38 cells were 4.217 µg/ml and 154.1 µg/ml, respectively. AgNPs induce an upregulation in the synthesis of inflammation-associated cytokines, including (TNF-α and IL-33), within HepG2 cells. AgNPs co-treatment led to higher glutathione levels and activating pro-autophagic genes such as AMPK.Additionally, it resulted in the suppression of mTOR, MMP-9, BCL-2, and α-SMA gene expression. The docking experiments suggest that the binding of AgNPs to the active site of the AMPK enzyme leads to inhibiting its activity. The inhibition of AMPK ultimately results in the suppression of the mechanistic mTOR and triggers apoptosis in HepG2 cells. In conclusion, the results of our study indicate that the utilization of AgNPs may represent a viable strategy for the eradication of liver cancerous cells through the activation of apoptosis and the enhancement of immune system reactions.

Biogenic selenium nanoparticles and selenium/chitosan-Nanoconjugate biosynthesized by Streptomyces parvulus MAR4 with antimicrobial and anticancer potential.

BACKGROUND: As antibiotics and chemotherapeutics are no longer as efficient as they once were, multidrug resistant (MDR) pathogens and cancer are presently considered as two of the most dangerous threats to human life. In this study, Selenium nanoparticles (SeNPs) biosynthesized by Streptomyces parvulus MAR4, nano-chitosan (NCh), and their nanoconjugate (Se/Ch-nanoconjugate) were suggested to be efficacious antimicrobial and anticancer agents. RESULTS: SeNPs biosynthesized by Streptomyces parvulus MAR4 and NCh were successfully achieved and conjugated. The biosynthesized SeNPs were spherical with a mean diameter of 94.2 nm and high stability. Yet, Se/Ch-nanoconjugate was semispherical with a 74.9 nm mean diameter and much higher stability. The SeNPs, NCh, and Se/Ch-nanoconjugate showed significant antimicrobial activity against various microbial pathogens with strong inhibitory effect on their tested metabolic key enzymes [phosphoglucose isomerase (PGI), pyruvate dehydrogenase (PDH), glucose-6-phosphate dehydrogenase (G6PDH) and nitrate reductase (NR)]; Se/Ch-nanoconjugate was the most powerful agent. Furthermore, SeNPs revealed strong cytotoxicity against HepG2 (IC50 = 13.04 µg/ml) and moderate toxicity against Caki-1 (HTB-46) tumor cell lines (IC50 = 21.35 µg/ml) but low cytotoxicity against WI-38 normal cell line (IC50 = 85.69 µg/ml). Nevertheless, Se/Ch-nanoconjugate displayed substantial cytotoxicity against HepG2 and Caki-1 (HTB-46) with IC50 values of 11.82 and 7.83 µg/ml, respectively. Consequently, Se/Ch-nanoconjugate may be more easily absorbed by both tumor cell lines. However, it exhibited very low cytotoxicity on WI-38 with IC50 of 153.3 µg/ml. Therefore, Se/Ch-nanoconjugate presented the most anticancer activity. CONCLUSION: The biosynthesized SeNPs and Se/Ch-nanoconjugate are convincingly recommended to be used in biomedical applications as versatile and potent antimicrobial and anticancer agents ensuring notable levels of biosafety, environmental compatibility, and efficacy.

Antimicrobial activity of certain natural-based plant oils against the antibiotic-resistant acne bacteria.

The unceasing emerging of multidrug-resistant bacteria imposes a global foremost human health threat and discovery of new alternative remedies are necessity. The use of plant essential oil in the treatment of many pathogenic bacteria is promising. Acne vulgaris is the most common skin complaint that fears many people about their aesthetic appearance. In this work we investigated the antibacterial activity of some plant oils against acne-inducing bacteria. Three bacterial isolates were identified from Egypt, biochemically and by means of 16s rRNA gene typing, and were designated as Staphylococcus aureus EG-AE1, Staphylococcus epidermidis EG-AE2 and Cutibacterium acnes EG-AE1. Antibiotic susceptibility test showed resistance of the isolates to at least six antibiotics, yet they are still susceptible to the last resort Vancomycin. In vitro investigations of eleven Egyptian plant oils, identified tea tree and rosemary oils to exhibit antibacterial activity against the antibiotic-resistant acne isolates. Inhibition zones of 15 ± 0.5, 21.02 ± 0.73 and 20.85 ± 0.76 mm was detected when tea tree oil applied against the above-mentioned bacteria respectively, while inhibition zones of 12.5 ± 1.5, 15.18 ± 0.38 and 14.77 ± 0.35 mm were detected by rosemary oils. Tea tree and rosemary oils exhibited bacteriostatic and bactericidal activity against all the strains with MICs/MBCs ranging between 39-78 mg/L for tea tree oil and 39-156 mg/L for rosemary oil. All the isolates were killed after 4 and 6 h upon growing with 200 mg/L of tea tree and rosemary oils, respectively. Additionally, gas chromatography mass spectrometry (GC/MS) profiling identified and detected a variable number of antimicrobial compounds in both oils.