Antibacterial Properties of Mesoporous Silica Nanoparticles Modified with Fluoroquinolones and Copper or Silver Species

Antibiotic resistance is a global problem and bacterial biofilms contribute to its development. In this context, this study aimed to perform the synthesis and characterization of seven materials based on silica mesoporous nanoparticles functionalized with three types of fluoroquinolones, along with Cu2+ or Ag+ species to evaluate the antibacterial properties against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa, including clinical and multi-drug-resistant strains of S. aureus and P. aeruginosa. In addition, in order to obtain an effective material to promote wound healing, a well-known proliferative agent, phenytoin sodium, was adsorbed onto one of the silver-functionalized materials. Furthermore, biofilm studies and the generation of reactive oxygen species (ROS) were also carried out to determine the antibacterial potential of the synthesized materials. In this sense, the Cu2+ materials showed antibacterial activity against S. aureus and E. coli, potentially due to increased ROS generation (up to 3 times), whereas the Ag+ materials exhibited a broader spectrum of activity, even inhibiting clinical strains of MRSA and P. aeruginosa. In particular, the Ag+ material with phenytoin sodium showed the ability to reduce biofilm development by up to 55% and inhibit bacterial growth in a “wound-like medium” by up to 89.33%.We gratefully acknowledge funding from the research project RTI2018-094322-B-I00 financed by MCIN/AEI/10.13039/501100011033/ and “ERDF A way of making Europe”, the Research Thematic Network RED2022-134091-T financed by MCIN/AEI/10.13039/501100011033, the University of the Basque Country UPV/EHU (GIC18/143) and (GIU20/028) and the Gobierno Vasco/Eusko Jaurlaritza (IT1755-22)

Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice

BACKGROUND: Cleft palate (CP) constitutes the most frequently seen orofacial cleft and is often associated with low folate status. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis, repair, and methylation. Whether the administration of isolated folic acid (FA) supplements prevents the CP caused by genetic mutations is unknown, as is its effect on the mechanisms leading to palate fusion. METHODS: FA was administered to females from two different strains of transforming growth factor β3 heterozygous mice. Null mutant progeny of these mice exhibit CP in 100% of cases of varying severity. We measured cleft length, height of palatal shelf adhesion, and the number of proliferating mesenchymal cells. Immunohistochemistry was also carried for collagen IV, laminin, fibronectin, cytokeratin-17, and EGF. RESULTS: FA supplementation significantly reduced CP severity and improved palatal shelf adhesion in both strains both in vivo and in vitro. Medial edge epithelium proliferation increased, and its differentiation was normalized as indicated by the presence and disposition of collagen IV, laminin, fibronectin, and cytokeratin-17. CONCLUSIONS: A maternal FA supplementation reduces the CP appearance by improving the mechanisms leading to palatal shelf adhesion.Ministerio de Economía y Competitividad de EspañaBanco SantanderUniversidad Complutense de MadridDepto. de Anatomía y EmbriologíaFac. de MedicinaTRUEpu

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice

[Purpose]: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice.[Materials and methods]: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan–Meier method, was performed, and association with various independent variables was assessed using Cox regression.[Results]: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07–3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77–9.92; P < .001).[Conclusion]: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy