Micro-crack formation and resultant bacterial infiltration are major causes of secondary caries formation in dental resin-based composite restorations. Improving dental resin composites’ mechanical and biological properties using highly bendable nanoparticles (NPs) can resolve this issue. This study aims to develop novel Diethylaminoethyl (DEAE)-Dextran silver nanoparticles (AgNPs) and subsequently modify composite resins with these NPs to enhance their mechanical and antibacterial properties. DEAE-Dextran AgNPs were successfully synthesized using a chemical reduction method that was confirmed with the help of ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Zeta potential, and energy-dispersive X-ray spectroscopy (EDS). Antibacterial activity of a composite disc with DEAE-Dextran AgNPs was tested against Streptococcus mutans, Enterococcus faecalis, and oral microcosm. The composite discs prepared with DEAE-Dextran AgNPs exhibited excellent antibacterial activity compared with composite resin reinforced by simple AgNPs (p < 0.05). Mechanical properties were significantly enhanced by adding DEAE-Dextran into composite resin (p < 0.05). Moreover, unlike AgNPs, DEAE-Dextran AgNPs were found to be less hemolytic. The results establish strong ground applications for DEAE-Dextran-modified dental composite resins in restorative dental applications.
Doped Zinc oxide (ZnO) Nanoparticles (NPs) have been widely studied in a variety of diagnostic and therapeutic applications. However, transition metal doped ZnO NPs have been rarely explored as an antibacterial agent in dental restorative materials. This study aimed to synthesize and characterize ZnO NPs doped with transition metals i.e. Copper (Cu) and Silver (Ag) and enhancement of resin composite with these NPs to evaluate their antibacterial and mechanical properties. Cu/ZnO NPs and Ag/ZnO NPs of 23.6 and 20.5 nm respectively, were successfully prepared by coprecipitation method, and confirmed by UV-vis spectroscopy, Scanning Electron Microscopy (SEM), Energy dispersive X-ray (EDX), Fourier transform infrared (FTIR). After successful doping, varying concentrations of bare and doped NPs were added into the composite. The composite disks were then exposed to S.mutans, in a closed system in vitro biofilm model followed by assessment of Colony-forming units (CFU/mL) to realize the antibacterial activity. To analyze mechanical properties, compressive strength analysis was carried out using a universal testing machine. The biocompatibility was evaluated by performing a hemocompatibility test. The composites with both Cu/ZnO and Ag/ZnO NPs exhibited enhanced antibacterial activity compared to composites with bare ZnO NPs at all concentrations. However, at higher concentrations of doped ZnO NPs, the aesthetics of the composites were compromised. In summary, this study demonstrated that transition metal doped ZnO NPs, specifically Ag/ZnO at 1% concentration can be used as antibacterial agent in dental restorative materials without affecting their biocompatibility and mechanical strength.
Typhoid fever, caused by Salmonella enterica serovar typhi , presents a substantial global health threat, particularly in regions with limited healthcare infrastructure. The rise of multidrug-resistant strains of S. typhi exacerbates this challenge, severely compromising conventional treatment efficacy due to over activity of efflux pumps. In our study, a comprehensive exploration of two fundamental aspects to combat MDR in S. typhi is carried out; i.e. employing advanced bioinformatics analyses and AlphaFold AI, We successfully identified and characterised a putative homologue, ABC-TPA, reminiscent of the P-glycoprotein (P-gp) known for its role in multidrug resistance in diverse pathogens. This discovery provides a critical foundation for understanding the potential mechanisms driving antibiotic resistance in S. typhi . Furthermore, employing computational methodologies, We meticulously assessed the potential of lignans, specifically Schisandrin A, B, and C, as promising Efflux Pump Inhibitors (EPIs) against the identified P-gp homologue in S. typhi . Noteworthy findings revealed robust binding interactions of Schisandrin A and B with the target protein, indicating substantial inhibitory capabilities. In contrast, Schisandrin C exhibited instability, showing varied effectiveness among the evaluated lignans. Pharmacokinetics and toxicity predictions underscored the favourable attributes of Schisandrin A, including prolonged action duration. Furthermore, high systemic stability and demanished toxicity profile of SA and SB present their therapeutic efficacy against MDR. This comprehensive investigation not only elucidates potential therapeutic strategies against MDR strains of S. typhi but also highlights the relevance of computational approaches in identifying and evaluating promising candidates. These findings lay a robust foundation for future empirical studies to address the formidable challenges antibiotic resistance poses in this clinically significant infectious diseases.
Pseudomonas aeruginosa is a Gram-negative pathogenic bacterium that is present commonly in soil and water and is responsible for causing septic shock, pneumonia, urinary tract and gastrointestinal infections, etc. The multi-drug resistance (MDR) phenomenon has increased dramatically in past years and is now considered a major threat globally, so there is an urgent need to develop new strategies to overcome drug resistance by P. aeruginosa. In P. aeruginosa, a major factor of drug resistance is associated to the formation of biofilms by the LasR enzyme, which regulates quorum sensing and has been reported as a new therapeutic target for designing novel antibacterial molecules. In this study, virtual screening and molecular docking were performed against the ligand binding domain (LBD) of LasR by employing a pharmacophore hypothesis for the screening of 2373 FDA-approved compounds to filter top-scoring hit compounds. Six inhibitors out of 2373 compounds were found to have binding affinities close to that of known LasR inhibitors. The binding modes of these compounds to the binding site in LasR-LBD were analyzed to identify the key interactions that contribute to the inhibition of LasR activity. Then, 50 ns simulations of top hit compounds were performed to elucidate the stability of their binding conformations with the LasR-LBD. This study, thus concluded that sulfamerazine showed the highest binding affinity for the LasR-LBD binding pocket exhibiting strong inhibitory binding interactions during molecular dynamics (MD) simulation.
Plant phytochemicals have potential decontaminating properties, however, their role in the amelioration of hydrophobic water filtration membranes have not been elucidated yet. In this work, phytochemicals (i.e., cannabinoids (C) and terpenes (T) from C. sativa) were revealed for their antibacterial activity against different Gram-positive and Gram-negative bacteria. As such, a synergistic relationship was observed between the two against all strains. These phytochemicals individually and in combination were used to prepare polyethersulfone (PES) hybrid membranes. Membrane characterizations were carried out using scanning electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy. Moreover, contact angle, water retention, surface roughness, mechanical testing, and X-ray florescence analysis were also carried out. According to results, the CT-PES hybrid membrane exhibited the lowest contact angle (40°), the highest water retention (70%), and smallest average pore size (0.04 µm). The hybrid membrane also exhibited improved water flux with no surface leaching. Quantitative bacterial decline analysis of the CT-PES hybrid membranes confirmed an effective antibacterial performance against Gram-positive and Gram-negative bacteria. The results of this study established cannabinoids and terpenes as an inexpensive solution for PES membrane surface modification. These hybrid membranes can be easily deployed at an industrial scale for water filtration purposes.
Multidrug resistance (MDR) has been a potentiator for the exploration of antibiotics. Nano drug delivery systems have opened new avenues to overcome this challenge. Although antibacterial nanocarriers are extensively realized, their effect on the bacteria residing inside the tissues and their toxicity is rarely explored. This study investigated the effects of flavonoid coated gold nanoparticles (FAuNPs) on the colonization of Enterococcus faecalis in the mouse liver and kidneys. Flavonoids were extracted from the leaves of Berberis lycium Royle and used to stabilize gold following a green synthesis approach. FAuNPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning transmission electron microscopy (STEM), X-ray powder diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS). FAuNPs showed significantly higher reduction in bacterial counts in in-vitro and in-vivo in mice organs as compared to the free flavonoids owing to their biocompatibility and effectiveness.
Resin composites have been widely used in dental restoration. However, polymerization shrinkage and resultant bacterial microleakage are major limitations that may lead to secondary caries. To overcome this, a new type of antibacterial resin composite containing ciprofloxacin-loaded silver nanoparticles (CIP-AgNPs) were synthesized. The chemical reduction approach successfully produced CIP-AgNPs, as demonstrated by FTIR, zeta potential, scanning electron microscopy, and ultraviolet-visible (UV-vis) spectroscopy. CIP-AgNPs were added to resin composites and the antibacterial activity of the dental composite discs were realized against Enterococcus faecalis, Streptococcus mutans, and the Saliva microcosm. The biocompatibility of modified resin composites was assessed and mechanical testing of modified dental composites was also performed. The results indicated that the antibacterial activity and compressive strength of resin composites containing CIP-AgNPs were enhanced compared to the control group. They were also biocompatible when compared to resin composites containing AgNPs. In short, these results established strong ground application for CIP-AgNP-modified dental composite resins.
Synthetic periodontal membranes have appeared as a promising treatment modality for periodontal disease. They provide a suitable site for attachment and growth environment for periodontal cells and exhibit high biocompatibility and high water retaining capacity. However, existing membranes can develop biofilms and induce inflammation at the periodontal pocket and gingival cells, hence limiting their effectiveness. A Polycaprolactone/sodium alginate-based core-shell membrane with Magnesium doped Zinc oxide (PCL/SA/MgZnO) nanoparticles (NPs) was developed, with initial burst release followed by sustained release of the antibacterial agent. The membrane was synthesized using casting and dip coating methods and characterized using Scanning Electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The membranes were then evaluated for their antibacterial potential against Enterococcus faecalis, Streptococcus mutans, saliva microcosm, and diabetic saliva microcosm. Furthermore, they were analyzed for water-retaining capacity as well as mechanical properties and biocompatibility. The membranes were finally tested in a novel alloxan-induced diabetic periodontal rodent model based on the coinfection of E. faecalis and S. mutans. The results showed the enhanced antibacterial potential of PCL/SA/MgZnO membranes against E. faecalis, S. mutans, saliva microcosm, and diabetic saliva microcosm. The PCL/SA/MgZnO exhibited better mechanical strength as compared to PCL/SA and PCL/SA/ZnO membranes. The histological findings showed reduced inflammation in diabetic rats with periodontitis treated with PCL/SA/MgZnO. Furthermore, periodontal regeneration was also observed in the X-ray radiographs of rats treated with PCL/SA/MgZnO membranes. The PCL/SA-based core-shell membranes with MgZnO are effective candidates for the treatment of periodontal biofilms and inflammation in high-risk patients such as diabetic patients.
The adverse effects of anticancer drugs, the acquired drug resistance, and tumor heterogeneity among cancer patients limit the effective clinical management of advanced malignancies. To overcome these challenges, predictive biomarkers emerged as an indispensable tool to aid medical oncologists in identifying cancer patients who may respond to several anticancer therapies, hence increasing the risk-to-benefit ratio. This chapter will offer a brief overview of predictive anticancer biomarkers, their characteristics, and brief details about the tools and techniques in practice for their identification. This chapter will also discuss the validated and also commonly researched predictive anticancer biomarkers for anticancer drugs against different cancer types. Finally, the challenges in identification and commercialization of the predictive biomarkers for anticancer drugs will be discussed.
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