Radiation enteritis is a frequently encountered issue for patients receiving radiotherapy and has a significant impact on cancer patients' quality of life. The gut microbiota plays a pivotal role in intestinal function, yet the impact of irradiation on gut microorganisms is not fully understood. This study explores the gastroprotective effect and gut microbiome-modulating potential of ubiquinol (Ubq), the reduced form of the powerful antioxidant CoQ-10. For this purpose, male albino rats were randomly assigned to four groups: Control, IRR (acute 7 Gy γ-radiation), Ubq_Post (Ubq for 7 days post-irradiation), and Ubq_Pre/Post (Ubq for 7 days pre and 7 days post-irradiation). The fecal microbiomes of all groups were profiled by 16S rRNA amplicon sequencing followed by bioinformatics and statistical analysis. Histopathological examination of intestinal tissue indicated severe damage in the irradiated group, which was mitigated by ubiquinol with enhanced regeneration, goblet cells, and intestinal alkaline phosphatase expression. Compared to the irradiated group, the Ubq-treated groups had a significant recovery of intestinal interleukin-1β, caspase-3, nitric oxide metabolites, and thio-barbituric reactive substances to near-healthy levels. Ubq_Pre/Post group displayed elevated peroxisome proliferator-activated receptor (PPAR-γ) level, suggesting heightened benefits. Serum insulin reduction in irradiated rats improved post-Ubq treatment, with a possible anti-inflammatory effect on the pancreatic tissue. Fecal microbiota profiling revealed a dysbiosis state with a reduction of bacterial diversity post-irradiation, which was re-modulated in the Ubq treated groups to profiles that are indistinguishable from the control group. These findings underscore Ubq's gastroprotective effects against radiation-induced enteritis and its potential in restoring the gut microbiota’s diversity and balance.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections which, due to the spread of antimicrobial resistance, have become increasingly serious. Bacterial skin infection affects the barrier function of skin causing depletion of the ceramide content in the stratum corneum (SC) of the epidermis. In the study reported herein, luteolin (LUT) a naturally-occurring flavonoid was incorporated in PEGylated cerosomes (PCs) to boost its antibacterial action as a topical application. The opimal formulation of the surface-modified lipidic vesicles was chosen with the aid of a 2³ full factorial design. The effectiveness of the optimal LUT formulation which was developed was evaluated using several MRSA strains both in vitro and in vivo studies. Results: A 2³ full factorial design was employed for the preparation of the optimum PC formulation, designated herein as F5. A comparative in vitro release study revealed the superiority of F5 over a LUT suspension in solubilizing and releasing after 24 h, a higher percentage 78.1 ± 1.8% of luteolin compared with only 18.3 ± 2.1% for the luteolin suspension. When tested against MRSA strains, F5 showed antimicrobial activity that was higher than that of the luteolin suspension, having a MIC value of 187.5 µg/mL versus 1500 µg/mL. In addition to having enhanced anti-virulence activity than the luteolin suspension in terms of antibiofilm formation (with % inhibition ranging from 45 to 99% with the tested strains at 0.5 × and 0.25 × MICs, where the luteolin suspension only had a range from 1 to 45%), enhanced anti-pigment production, and anti-α-hemolysin activity were also observed. Moreover, F5 affected the cell wall integrity as confirmed by transmission electron microscopy (TEM). Scanning electron microscopy (SEM) verified the effect of F5 on bacterial biofilm formation, showing reduction of cellular adhesion and disruption of biofilm, factors which greatly contribute to bacterial pathogenesis and antibiotic resistance. When compared to the negative control and the luteolin suspension groups, the F5 formulation also resulted in reducing the bacterial load in the murine skin infection model. Conclusions: F5 PEGylated cerosomes are potential new potent defense agents against MRSA infections, demonstrating promising therapeutic capabilities.

Background: One of the main issues facing public health with microbial infections is antibiotic resistance. Nanoparticles (NPs) are among the best alternatives to overcome this issue. Silver nanoparticle (AgNPs) preparations are widely applied to treat multidrug-resistant pathogens. Therefore, there is an urgent need for greater knowledge regarding the effects of improper and excessive use of these medications. The current study describes the consequences of long-term exposure to sub-lethal concentrations of AgNPs on the bacterial sensitivity to NPs and the reflection of this change on the bacterial genome. Results: Chemical methods have been used to prepare AgNPs and gamma irradiation has been utilized to produce more stable AgNPs. Different techniques were used to characterize and identify the prepared AgNPs including UV-visible spectrophotometer, Fourier Transform Infrared (FT-IR), Dynamic light scattering (DLS), and zeta potential. Transmission electron microscope (TEM) and Scanning electron microscope (SEM) showed 50–100 nm spherical-shaped AgNPs. Eleven gram-negative and gram-positive bacterial isolates were collected from different wound infections. The minimum inhibitory concentrations (MICs) of AgNPs against the tested isolates were evaluated using the agar dilution method. This was followed by the induction of bacterial resistance to AgNPs using increasing concentrations of AgNPs. All isolates changed their susceptibility level to become resistant to high concentrations of AgNPs upon recultivation at increasing concentrations of AgNPs. Whole genome sequencing (WGS) was performed on selected susceptible isolates of gram-positive Staphylococcus lentus (St.L.1), gram-negative Klebsiella pneumonia (KP.1), and their resistant isolates St.L_R.Ag and KP_R.Ag to detect the genomic changes and mutations. Conclusions: For the detection of single-nucleotide polymorphisms (SNPs) and the identification of all variants (SNPs, insertions, and deletions) in our isolates, the Variation Analysis Service tool available in the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) was used. Compared to the susceptible isolates, the AgNPs-resistant isolates St.L_R.Ag and KP_R.Ag had unique mutations in specific efflux pump systems, stress response, outer membrane proteins, and permeases. These findings might help to explain how single-nucleotide variants contribute to AgNPs resistance. Consequently, strict regulations and rules regarding the use and disposal of nano waste worldwide, strict knowledge of microbe-nanoparticle interaction, and the regulated disposal of NPs are required to prevent pathogens from developing nanoparticle resistance.