Synergistic effects of nano curcumin mediated photodynamic inactivation and nano-silver@colistin against Pseudomonas aeruginosa biofilms.

BACKGROUND: Patients with burn injuries colonized by multidrug-resistant Pseudomonas aeruginosa face increased mortality risk. The efficacy of colistin, a last-resort treatment, is declining as resistance levels rise. P. aeruginosa's robust biofilm exacerbates antibiotic resistance. Photodynamic Inactivation (PDI) shows promise in fighting biofilm. MATERIALS AND METHODS: Nano curcumin (nCur) particles were synthesized, and their chemical characteristics were determined using zeta potential (ZP), dynamic light scattering analysis (DLS), energy-dispersive X-ray (EDX) analysis, and fourier transform infrared (FTIR). We conducted an MTT assay to assess the cytotoxicity of nCur-mediated PDI in combination with nanosilver colistin. The fractional biofilm inhibitory concentration (FBIC) of two P. aeruginosa clinical isolates and P. aeruginosa ATCC 27853 during nCur-mediated PDI@AgNPs@CL was determined using a 3-dimensional (3-D) checkerboard assay. To study the effect of nCur-mediated PDI@AgNPs@CL on lasI, lasR, rhlI, rhlR, pelA, and pslA gene expression, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted at each isolate's FBIC. The impact of treatments was also investigated using scanning electron microscopy (SEM). RESULTS: The ZP and mean DLS values of the nCur were 10.3 mV and 402.6 ± 24.6 nm, respectively. The distinct functional groups of nCur corresponded with the peaks of FTIR absorption. Moreover, the EDX analysis showed the ratios of different metals in nCur. Cell viability percentages of nCur-mediated PDI@AgNPs@CL at FBIC concentrations of clinical isolates Nos. 30, 354, and P. aeruginosa ATCC 27853 were 91.36 %, 83.20 %, and 92.48 %, respectively. nCur-mediated PDI@AgNPs@CL treatment showed synergistic effects in clinical isolates and P. aeruginosa ATCC 27853 in a 3-D checkerboard assay. All six of the investigated genes showed down-regulation after nCur-mediated PDI@AgNPs@CL treatment. The most suppressed gene during nCur-mediated PDI@AgNPs@CL treatment was the rhlR gene (-11.9-fold) of P. aeruginosa ATCC 27853. The SEM micrographs further proved the connecting cement reduction and biofilm mass mitigation following nCur-mediated PDI@AgNPs@CL treatments. CONCLUSIONS: The combined effect of nCur-mediated PDI and AgNPs@CL synergistically reduce the formation of biofilm in P. aeruginosa. This may be attributable to the suppression of the genes responsible for regulating the production of biofilms.

Dimedone nanoparticle as a promising approach against toxoplasmosis: In vitro and in vivo evaluation.

Toxoplasma gondii, an intracellular parasite, has shown drug resistance and therapeutic failure in recent years. Dimedone (DIM) has been introduced as a new chemical compound with anti-bacterial and anti-cancer properties. The aim of this study was to investigate the potential protective role of DIM nanoparticles in an animal model of toxoplasmosis. Cytotoxicity of DIM on Vero cell line assessed using MTT, and the effect of DIM on Toxoplasma gondii was evaluated by counting the number of parasites compared to the control group in vitro. The rate of pathogenesis and virulence of the parasite was checked on the liver cells of the animal model using hematoxylin-eosin staining. Furthermore, various parameters indicating oxidative stress were compared in mouse liver tissue in different groups. The release of the nanoparticle form was significantly longer than the free drugs. The IC50 of Nano-DIM was 60 µM and the reduction of intracellular parasite proliferation in the group Nano-DIM and Nano-PYR (Nano-primethamine) was significantly lower than the free drugs in vitro. Histopathology examination in the groups treated with dimedone nanomedicine showed that the degree of disintegration of the epithelium of the central vein of the liver and infiltration and vacuolization of liver cells were lower compared to the toxoplasmosis group. Additionally, the level of some oxidative stress indicators was observed to be lower in the nano-treated groups compared to other groups. The results of this study showed DIM can be used as a promising compound for anti-T. gondii activity and can prevent the proliferation of it in cells.

Nano drug delivery in intracellular bacterial infection treatments.

The present work aimed to review the potential mechanisms used by macrophages to kill intracellular bacteria, their entrance to the cell, and mechanisms of escape of cellular immunity and applications of various nanoparticles. Since intracellular bacteria such as Mycobacterium and Brucella can survive in host cells and can resist the lethal power of macrophages, they can cause chronic disease or recur in 10-30% of cases in improved patients Nano drug-based therapeutics are promising tools for treating intracellular bacteria and preventing recurrence of the disease caused by these bacteria. In addition, among their unique features, we can mention the small size and the ability of these compounds to purposefully reach the target location.

COVID-19: docking-based virtual screening and molecular dynamics study to identify potential SARS-CoV-2 spike protein inhibitors from plant-based phenolic compounds.

A novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters into the host cells through an interaction between its surface spike protein (S-protein) and the angiotensin-converting enzyme 2 receptors, leading to coronavirus disease 2019 (COVID-19). Using effective S-protein inhibitors may reduce the virulence of the virus. Molecular docking was performed to evaluate the binding affinity of 97 phenolic compounds (phenolics) with the SARS-CoV-2 S-protein receptor-binding domain (RBD). Molecular dynamics (MD) simulation was carried out to assess the stability of interactions between top-ranked compounds and S-protein RBD. Pharmacokinetics and toxicity of top-ranked inhibitors were also studied. Furthermore, the essential residues involved in ligand binding, based on the degree of each amino acid in the ligand-amino acid interaction (LAI) network for S-protein, were identified. Molecular docking and MD simulations were performed utilizing the AutoDock and Discovery Studio Client version, respectively. The LAI network was analyzed using the Cytoscape software. Pharmacokinetics and toxicity of top-ranked compounds were studied using bioinformatics webservers. It was estimated that nine of the studied phenolics can bind to the SARS-CoV-2 S-protein at the nanomolar scale with a considerable estimated energy of binding (∆G binding Keywords: COVID-19; drug; molecular docking; molecular dynamics; SARS-CoV-2; spike protein.

Antibacterial Effects of a 940 nm Diode Laser With/ Without Silver Nanoparticles Against Enterococcus faecalis.

Introduction: The final goal of root canal therapy is to remove of the most bacteria from the root canal. This study aimed at comparing the antibacterial effects of a diode laser with a wavelength of 940nm and silver nanoparticles and the synergic effects of both techniques on Enterococcus faecalis. Methods: Ninety single-rooted human teeth were decoronated and prepared with rotary files. The samples were irrigated with sodium hypochlorite and EDTA17%. Then they were autoclaved and contaminated with E. faecalis suspension (1.5 × 108 CFU/mL) for 21 days. The samples were fixed in a microtube and were randomly divided into 4 experimental (n=20) groups and a negative control group (n=10) as follows: Group 1: hypochlorite sodium 5%, Group 2: silver nanoparticle, Group 3: diode laser, and Group 4: diode laser and silver nanoparticle. The samples were obtained from dentin chips before and after the intervention. The data were analysed using the Kruskal-Wallis nonparametric test. Furthermore, alterations in bacterial colonies were entered using the Wilcoxon signed ranks test (α=0.05). Results: There was a significant decrease in colony counts for all groups after interventions (P value<0.05). Also, all groups showed more reductions in colony counts compared with the negative control group (P value <0.004). There was a significant reduction for group 1 in comparison with other groups (P value <0.001) and this group had an extreme decrease of colony counts (RCC=100%). There was an important differential between silver nanoparticles and diode laser groups in bacterial counts (P value<0.001) and silver nanoparticles (RCC=83.15%) had more efficiency than the diode laser (RCC=41/33%). RCC of group 4 was 68/52%. Conclusion: Followed by sodium hypochlorite 5%, silver nanoparticles were the most effective antibacterial substances. The 940 nm laser diode had less antibacterial effect compared to its use with silver nanoparticles.