Investigating the Antibacterial Effects of Synthetic Gamma-Lactam Heterocycles on Methicillin-Resistant Staphylococcus aureus Strains and Assessing the Safety and Effectiveness of Lead Compound MFM514.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be one of the main causes of hospital-acquired infections in all regions of the world, while linezolid is one of the only commercially available oral antibiotics available against this dangerous gram-positive pathogen. In this study, the antibacterial activity from 32 analogues of synthetic gamma-lactam heterocycles against MRSA was determined. Amongst screened analogues for the minimum inhibitory concentration (MIC) assay, compound MFM514 displayed good inhibitory activity with MIC values of 7.8-15.6 µg/mL against 30 MRSA and 12 methicillin-sensitive S. aureus (MSSA) clinical isolates, while cytotoxicity evaluations displayed a mean inhibitory concentration (IC50) value of > 625 µg/mL, displaying a potential to becoming as a lead compound. In subsequent animal studies for MFM514, a single-dose oral acute toxicity test revealed an estimated mean lethal dose (LD50) value of <5000 mg/kg, while in the mice infection test, a mean effective dose (ED50) value of 29.39 mg/kg was obtained via oral administration. These results suggest that gamma-lactam carbon skeleton, particularly MFM514, is highly recommended to be evaluated further as a new safe and efficacious orally delivered antibacterial agent against MRSA.

Waste Mineral Wool and Its Opportunities-A Review.

Massive waste rock wool was generated globally and it caused substantial environmental issues such as landfill and leaching. However, reviews on the recyclability of waste rock wool are scarce. Therefore, this study presents an in-depth review of the characterization and potential usability of waste rock wool. Waste rock wool can be characterized based on its physical properties, chemical composition, and types of contaminants. The review showed that waste rock wool from the manufacturing process is more workable to be recycled for further application than the post-consumer due to its high purity. It also revealed that the pre-treatment method-comminution is vital for achieving mixture homogeneity and enhancing the properties of recycled products. The potential application of waste rock wool is reviewed with key results emphasized to demonstrate the practicality and commercial viability of each option. With a high content of chemically inert compounds such as silicon dioxide (SiO2), calcium oxide (CaO), and aluminum oxide (Al2O3) that improve fire resistance properties, waste rock wool is mainly repurposed as fillers in composite material for construction and building materials. Furthermore, waste rock wool is potentially utilized as an oil, water pollutant, and gas absorbent. To sum up, waste rock wool could be feasibly recycled as a composite material enhancer and utilized as an absorbent for a greener environment.

In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA.

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.

Primary human monocyte differentiation regulated by Nigella sativa pressed oil.

BACKGROUND: Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil. METHODS: Primary human monocytes were isolated from whole blood and grown at 37°C and 5% CO2 saturation for five days prior to treatment with Nigella sativa oil. The cells were plated and washed before treatment with ox-LDL (10 µg/ml) as positive control and combined treatment of ox-LDL (10 µg/ml) and (140 ng/ml) Nigella sativa oil. The growth progression was monitored every 24 hours for 3 days. RESULTS: Macrophages showed reduced growth in comparison to monocytes 24 hours after treatment with Nigella sativa oil. The mean cell diameter was significantly different between untreated and treated condition in monocytes and macrophages (p < 0.001). Similarly, intracellular lipid accumulation was hindered in combined treatment with Nigella sativa oil. This was further supported by cell surface expression analysis, where CD11b was markedly reduced in cells treated with combination oxLDL and Nigella sativa oil compared to oxLDL alone. More cells differentiated into macrophage-like cells when monocytes were supplemented with oxidized LDL alone. CONCLUSIONS: The finding provides preliminary evidence on regulation of cell growth and differentiation in monocyte and monocyte-derived macrophages by Nigella sativa oil. Further investigations need to be conducted to explain its mechanism in human monocyte.