Angel Daniel Campos Juarez

Paracetamol is a widely used analgesic and antipyretic agent; however, its use is limited by minimal anti‐inflammatory activity and the risk of hepatotoxicity from prolonged oral use or in acute overdose. To address these limitations, four novel phosphorylated paracetamol analogs (2a–2d) were synthesized via a UV‐radical methodology and evaluated through integrated in silico, in vitro, and in vivo for anti‐inflammatory dermal approaches. Molecular docking suggested plausible binding interactions with COX‐1 and COX‐2 for all analogs. In vitro cytotoxicity assays in THP‐1 cells showed that 2a and 2b did not affect cell viability at 100 μM over 24 h. In a TPA‐induced acute ear edema model in CD1 male mice, 2a produced about 50% inhibition of edema at the lowest tested quantity (0.5 mg/ear), representing a fourfold potency advantage over indomethacin at the same amount, while 2b displayed significant anti‐inflammatory and vasoregulatory activity at higher quantities. Computational ADME profiling indicated that all analogs satisfy Lipinski’s drug‐likeness criteria and exhibit low predicted hERG channel risk. These results support N‐phosphorylation of 4‐aminophenol as a viable strategy to improve the topical anti‐inflammatory efficacy of paracetamol analogs.

Despite the favorable mechanical properties and biocompatibility of Ti-6Al-4V, surface modification remains essential to enhance osseointegration and ensure long-term clinical performance. To address this, TNTs arrays were grown on Ti-6Al-4V substrates by anodic oxidation in a fluoride-containing electrolyte. Structural characterization confirmed the formation of nanocrystalline Ti₂O with an average crystal size of 21.2 nm, while morphological analysis revealed uniform nanotube arrays with diameters of 85.39 ± 10.7 nm. Nanoindentation assays demonstrated an elastic modulus of 8.034 GPa, closely matching human cortical bone, thereby reducing the risk of stress shielding. In vitro assays using hFOB 1.19 osteoblasts showed that titanium oxide nanotubes (TNTs) surfaces significantly accelerated αVβ3 integrin expression, observed the higher difference at 48 h compared to smooth surfaces. Furthermore, proliferation assays with CFSE revealed enhanced cell division on TNT films, with maximum proliferation observed at 96 h. These findings indicate that anodized titanium oxide nanotube films not only improve the mechanical compatibility of Ti-6Al-4V with bone tissue but also promote integrin-mediated osteoblast adhesion and proliferation. The results highlight the potential of TNT coatings as a promising surface engineering approach for next-generation dental and orthopedic implants.

The γδ T cells belong to a subgroup of T cells known as non-conventional T cells due to their limited T cell receptor (TCR) repertoire and ability to recognize non-peptide antigens. They play a crucial role in combating infections and tumors. Vγ9Vδ2 T cells are typically activated by molecules containing diphosphate groups, collectively known as phosphoantigens (pAgs), through a non-canonical mechanism which involves the intracellular domain of butyrofilin (BTN)3A1 protein. However, no FDA-approved drugs have yet been shown to activate them, and the underlying cellular mechanisms remain unknown. In this study, we combined high-throughput virtual screening of an FDA-approved drug database with in vitro cellular assays to identify potential γδ T cells activators. Our findings demonstrate that Nitazoxanide (NTZ) and Tinidazole induce moderate elicited a statistically significant increase in interferon (IFN)-γ production of Vγ9Vδ2 T cells by their probably interaction with the pAg binding site of BTN3A1. Additionally, NTZ induces expression of CD107a, but only at the highest concentrations tested and promotes the upregulation of HLA-DR in total PBMCs and CD14⁺ monocytes. Blocking BTN3A with a specific antibody led to a marked reduction in all NTZ-induced activations. This work identifies NTZ as a previously unrecognized activator of γδ T cells, highlighting its immunomodulatory potential beyond its known clinical uses. These findings broaden our understanding of γδ T cells pharmacology and suggest new opportunities for drug repurposing and the design of novel chemical scaffolds. Further mechanistic studies will be essential to fully define how NTZ engages the BTN3A–γδ T cells axis.

The surface modification of dental implants with nanostructured films enables the development of the next generation of biomaterials that promote osseointegration. In this study, a uniform layer of titanium oxide nanotubes (TNTs) was successfully formed on a Ti-6Al-4V dental implant screw through anodic oxidation. TNTs were morphologically characterized by Scanning Electron Microscopy (SEM), obtaining dimensions of 64.88 ± 10 nm in diameter and 5.34 ± 5 µm in length. Additionally, a crystal size of 23.45 nm was determined by X-ray diffraction (XRD) analysis. The TNT layer on the dental implant screw was evaluated in an in vitro system in direct contact with human osteoblast cells (hFOB) for 24 h and 48 h, finding cell growth near to the screw threads. Further, the biocompatibility of the dental screw coated with TNTs was evaluated using a flow cytometric assay with 7-AAD, demonstrating that cell viability was not affected at 24 h and 48 h. This study opens the perspective of the study of inflammation and osseointegration induced by implants coated with TNTs.