The polymicrobial proliferation and development of complex biofilm morphologies by bacterial and fungal pathogens in the host are some of the key factors contributing to the failure of antimicrobial treatments. The polymicrobial interaction of Candida albicans and some bacterial species has been extensively studied in both in vitro and in vivo model systems. Alternative strategies for disrupting polymicrobial interaction and biofilm formation are constantly needed. Among several alternative strategies, the use of nanoparticles synthesized using a natural product in the treatment of microbial infection has been considered a promising approach. The current study aimed to synthesize gold nanoparticles (AuNPs) using a natural product, fucoidan, and to test their efficacy against mono and duo combinations of fungal (Candida albicans) and bacterial (Staphylococcus aureus/Streptococcus mutans) biofilms. Several methods were used to characterize and study Fu–AuNPs, including UV-vis absorption spectroscopy, FTIR, FE-TEM, EDS, DLS, zeta potential, and XRD. The concentration-dependent inhibition of early-stage biofilms and the eradication of mature biofilms of single species of C. albicans, S. aureus, and S. mutans have been observed. Early biofilms of a dual-species combination of C. albicans and S. aureus/S. mutans were also suppressed at an increasing concentration of Fu–AuNPs. Furthermore, Fu–AuNPs significantly eradicated the established mature biofilm of mixed species. The treatment method proposed in this study, which involves the use of marine-bioinspired nanoparticles, is a promising and biocompatible agent for preventing the growth of polymicrobial biofilms of bacterial and fungal pathogens.
Purpose: To assess the effectiveness and tolerability of cyclosporine ophthalmic emulsion (CsA) 0.05% in patients with moderate to severe dry eye disease in Korea.Methods: This was a prospective, multicenter, open-label, surveillance study of 392 Korean patients with moderate to severe dry eye disease who were treated with CsA 0.05% for three months.An assessment of effectiveness was performed at baseline, and after 1, 2, and 3 months.The primary effectiveness outcomes were changes in ocular symptoms and Schirmer score.The secondary effectiveness outcomes were a change in conjunctival staining, use of artificial tears, global evaluation of treatment, and patient satisfaction.The primary safety outcome was the incidence and nature of adverse events.Results: A total of 362 patients completed the study.After three months, all ocular symptom scores were significantly reduced compared to the baseline values, while the Schirmer scores were significantly increased relative to baseline (p < 0.0001).After three months, there were significant reductions from baseline in conjunctival staining (p < 0.01) and use of artificial tears (p < 0.0001).According to clinicians' global evaluations, most patients (>50%) experienced at least a 25% to 50% improvement in symptoms from baseline at each follow-up visit.The majority of patients (72.0%) were satisfied with the treatment results, and 57.2% reported having no or mild symptoms after treatment.The most common adverse events were ocular pain (11.0%).Conclusions: Our findings indicate that CsA 0.05% is an effective and tolerable treatment for dry eye disease in Korean clinical practice.
Endotoxic responses to bacterial lipopolysaccharide (LPS) are triggered by Toll-like receptor 4 (TLR4) and involve the production of inflammatory mediators, including interleukin-6 (IL-6), by macrophages. The detailed mechanism of IL-6 production by macrophages in response to LPS has remained unclear, however. We now show that LPS induces IL-6 synthesis in mouse peritoneal macrophages via the leukotriene B4 receptor BLT2. Our results suggest that TLR4–MyD88 signaling functions upstream of BLT2 and that the generation of reactive oxygen species (ROS) by NADPH oxidase 1 (Nox1) and consequent activation of the transcription factor nuclear factor (NF)-κB function downstream of BLT2 in this response. These results suggest that a TLR4–MyD88–BLT2–Nox1–ROS–NF-κB pathway contributes to the synthesis of IL-6 in LPS-stimulated mouse macrophages. A cascade of receptor binding and signaling systems allows bacterial endotoxins to cause dangerous inflammatory responses. Endotoxins, consisting of linked lipid and polysaccharide, are released from some bacterial cell walls when the bacteria begin to break down. They can stimulate excessive and potentially fatal blood poisoning and "endotoxic shock". This damaging process is mediated by the release of signaling molecules, including immune system proteins known as interleukins, by cells that the toxins bind to. Jae-Hong Kim and co-workers at Korea University in Seoul, South Korea, have uncovered key steps in the pathway leading to interleukin-6 release when the toxins bind to certain mouse white blood cells. These findings could contribute to understanding and prevention of the endotoxic shock that is a leading cause of death in critically ill patients.
The structure–activity relationship of the synthesized tirbanibulin derivatives was explored; para fluorination on the benzylamine part yielded promising outcomes in potency and pharmacokinetics.
The emergence of antibiotic resistance in microbial pathogens necessitates the development of alternative ways to combat the infections that arise. The current study used nanotechnology as an alternate technique to control virulence characteristics and biofilm development in Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, based on the acceptance and biocompatibility of the probiotic bacteria, we chose a lactic acid bacteria (LAB) for synthesizing two types of metallic nanoparticles (NPs) in this study. Using molecular techniques, the LAB strain C1 was isolated from Kimchi food samples and identified as Lactiplantibacillus sp. strain C1. The prepared supernatant from strain C1 was used to produce gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs). C1-AuNPs and C1-AgNPs were characterized physiochemically using a variety of instruments. C1-AuNPs and C1-AgNPs had spherical shapes and sizes of 100.54 ± 14.07 nm (AuNPs) and 129.51 ± 12.31 nm (AgNPs), respectively. C1-AuNPs and C1-AgNPs were discovered to have high zeta potentials of -23.29 ± 1.17 and -30.57 ± 0.29 mV, respectively. These nanoparticles have antibacterial properties against several bacterial pathogens. C1-AuNPs and C1-AgNPs significantly inhibited the initial stage biofilm formation and effectively eradicated established mature biofilms of P. aeruginosa and S. aureus. Furthermore, when P. aeruginosa was treated with sub-MIC levels of C1-AuNPs and C1-AgNPs, their different virulence features were significantly reduced. Both NPs greatly inhibited the hemolytic activity of S. aureus. The inhibition of P. aeruginosa and S. aureus biofilms and virulence features by C1-AuNPs and C1-AgNPs can be regarded as viable therapeutic strategies for preventing infections caused by these bacteria.
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