Cyclodextrins (CDs) have traditionally been recognized as excipients that enhance solubility and stability of drugs. However, growing evidence shows that CDs themselves can act as active therapeutic agents. Their unique supramolecular properties enable them to interact with biological membranes, mobilize cholesterol, and modulate immune responses. This review highlights four therapeutic areas where CDs demonstrate particular promise. First, in gene and mRNA therapy, cationic CD derivatives form nanoparticles that protect nucleic acids, promote endosomal escape, and achieve targeted delivery. Second, in neurodegenerative disorders such as Niemann–Pick type C and Alzheimer’s disease, hydroxypropyl-β-CD facilitates cholesterol clearance and reduces pathological lipid accumulation. Third, in detoxification, the γ-CD derivative sugammadex exemplifies a clinically approved agent that encapsulates neuromuscular blockers to reverse anesthesia. Finally, CDs have emerged as safe vaccine adjuvants, inducing robust systemic and mucosal immunity with reduced IgE responses compared to alum. Together, these examples illustrate a paradigm shift: CDs are not only versatile excipients but also active molecules with direct therapeutic effects. Future translation will require careful optimization of safety, scalability, and regulatory compliance, but CDs are poised to contribute meaningfully to next-generation medicines.

Orthopedic implants have a critical role in modern medical practice, being useful in bone regeneration, joint arthroplasty, and healing fractures. The success of osseointegration depends on implant properties (composition, stability, geometry, biocompatibility) and host factors (local reactivity, comorbidities). Preclinical evaluation in animal models is essential before clinical application. In orthopedic implantology, the selection and real utility of a range of animals are important, with an emphasis placed on bone–implant interface, biomechanical function, and long-term integration. Smaller animals such as rabbits and rats have widespread use in early biocompatibility and osseointegration testing, but larger animals such as pigs, sheep, and canines have a larger physiological bone similarity and can, therefore, be utilized for bearing loads in testing. Considering the utility and disadvantages of certain species—including suitability for new biomaterials, coatings, and biomechanical function—this article discusses testing methodologies such as push-out/pull-out tests, histomorphometry, and micro-CT and their utility in testing the integration of implants and regeneration of bone. Conclusions confirm a multi-species model in use in preclinical testing for the development of implants and improvements in clinical success. Unlike previous reviews, this article emphasizes translational strategies, integrates ethical perspectives in model selection, and discusses the synergistic use of imaging modalities with biomechanical tests for comprehensive assessment.

Background/Objectives: This review evaluates the expanding contributions of artificial intelligence (AI) across biomedicine, focusing on cancer therapy and nanomedicine, cardiology and medical imaging, neurodegenerative disorders, and liver disease. Core AI concepts (machine learning, deep learning, artificial neural networks, model training/validation, and explainability) are introduced to frame application domains. Methods: A systematic search of major biomedical databases (2010–2025) identified English-language original studies on AI in these four areas; 203 articles meeting PRISMA 2020 criteria were included in a qualitative synthesis. Results: In oncology and nanomedicine, AI-driven methods expedite nanocarrier design, predict biodistribution and treatment response, and enable nanoparticle-enhanced monitoring. In cardiology, algorithms enhance ECG interpretation, coronary calcium scoring, automated image segmentation, and noninvasive FFR estimation. For neurological disease, multimodal AI models integrate imaging and biomarker data to improve early detection and patient stratification. In hepatology, AI supports digital histopathology, augments intraoperative robotics, and refines transplant wait-list prioritization. Common obstacles are highlighted, including data heterogeneity, lack of standardized acquisition protocols, model transparency, and the scarcity of prospective multicenter validation. Conclusions: AI is emerging as a practical enabler across these biomedical fields, but its safe and equitable use requires harmonized data, rigorous multicentre validation, and more transparent models to ensure clinical benefit while minimizing bias.

Background/Objectives: The present study aims to highlight the possible significant changes due to the COVID-19 pandemic in the resistance of pathogens involved in cases of pediatric infections. Methods: This study included children hospitalized in the Pediatric Intensive Care Unit, Surgery and Pediatrics from a tertiary teaching hospital, during and after the COVID-19 period (2020–2023). Results: The research included 845 samples collected during 2020–2023, from 685 pediatric patients. A total of 937 bacterial isolates were obtained, of which 509 isolates (54.32%) were Gram-negative bacteria. Around 30% of all the pathogens were multidrug-resistant (MDR), with a statistically significant increase post-pandemic, in the case of the MDR Escherichia coli strains (p < 0.05). A very high percentage of MDR Acinetobacter spp. isolates was found, with an important, but not statistically significant, increase in the post-pandemic period. The highest percentage of the MDR Gram-positive pathogens was registered in the case of S. aureus strains (31.80%). Over 20% of the Coagulase-negative Staphylococci (CoNS) strains isolated between 2020 and 2023 were MDR, with an important increase in the post-COVID-19 period. The proportion of carbapenem-resistant Gram-negative pathogens significantly decreased in the post-COVID-19 period compared with the COVID-19 period (p < 0.05), especially in the case of the Klebsiella spp. strains. Conclusions: Our findings revealed the increase in the post-COVID-19 period of the prevalence of MDR strains of Acinetobacter spp., CoNS, and Escherichia coli isolated in pediatric patient samples and a significant decline in the trend of the carbapenem-resistant Gram-negative pathogens, which may be due to the testing rate and to the specific pathology of the pediatric patients hospitalized in the two periods.

This review critically examines how cyclodextrins modulate regulated cell death pathways and the implications for immunometabolism and therapeutic translation. Increasing evidence, however, indicates that cyclodextrins exert intrinsic biological activity by modulating cellular lipid homeostasis, membrane organization, and intracellular trafficking. In recent years, these properties have positioned cyclodextrins as unexpected regulators of regulated cell death (RCD) pathways, with broad implications for immunometabolism and therapeutic innovation. This review provides a comprehensive overview of the mechanisms by which native and chemically modified cyclodextrins influence major forms of regulated cell death, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis, and necroptosis. Particular attention is given to cholesterol sequestration, lipid raft disruption, lysosomal cholesterol mobilization, and transcriptional reprogramming via pathways such as TFEB (transcription factor EB) and AMPK (AMP-activated protein kinase), which collectively shape cell fate decisions. We further examine how cyclodextrin-mediated modulation of RCD intersects with immune metabolism, especially macrophage polarization and inflammasome activity, thereby influencing inflammatory responses and disease progression. Translational implications are discussed across diverse pathological contexts, including cancer, cardiovascular diseases, neurodegenerative disorders, inflammatory and autoimmune conditions, infectious diseases, and lysosomal storage disorders. Finally, emerging cyclodextrin-based delivery platforms, ranging from inclusion complexes to nanoparticles and polymeric systems, are evaluated with respect to their ability to achieve targeted modulation of cell death while minimizing off-target toxicity. Importantly, we critically discuss dose-dependent cytotoxicity, sterol depletion–related adverse effects, and formulation-dependent variability, which currently limit the clinical translation of cyclodextrin-mediated cell death modulation. By integrating mechanistic insights with pharmaceutical formulation strategies, this review delineates key challenges and opportunities for the rational design of cyclodextrin-based therapeutics. Overall, this review highlights cyclodextrins as bioactive modulators rather than inert carriers, underscoring their potential to inspire novel pharmacological strategies that integrate drug delivery, immunometabolism, and regulated cell death.

Background/Objectives: Hydroxyapatite (HAp)-based implants and HAp–titanium (HApTi) composites are widely used in orthopedic and dental applications, but their long-term success is limited by peri-implant bone loss. Local delivery of osteoactive molecules from implant surfaces may enhance osseointegration and reduce periprosthetic osteolysis. This study combined in silico modeling and experimental assays to compare calcium fructoborate (CaFb), sodium alendronate, and calcium alendronate as functionalization agents for HAp and HApTi implants. Methods: Molecular docking (AutoDock 4.2.6) and 100 ns molecular dynamics (MD) simulations (AMBER14 force field, SPC water model) were performed to characterize ligand–substrate interactions and to calculate binding free energies (ΔG_binding) and root mean square deviation (RMSD) values for ligand–HAp/HApTi complexes. HAp and HApTi discs obtained by powder metallurgy were subsequently functionalized by surface adsorption with CaFb or alendronate salts. The amount of adsorbed ligand was determined gravimetrically, and in vitro release profiles were quantified by HPTLC–MS for CaFb and by HPLC after FMOC derivatization for alendronates. Results: CaFb–HAp and CaFb–HApTi complexes showed the lowest binding free energies (−1.31 and −1.63 kcal/mol, respectively), indicating spontaneous and stable interactions. For HAp-based complexes, the mean ligand RMSD values over 100 ns were 0.27 ± 0.17 nm for sodium alendronate, 0.72 ± 0.28 nm for calcium alendronate (range 0.35–1.10 nm), and 0.21 ± 0.19 nm for CaFb (range 0.15–0.40 nm). For HApTi-based complexes, the corresponding RMSD values were 0.30 ± 0.15 nm for sodium alendronate, 0.72 ± 0.38 nm for calcium alendronate and 0.26 ± 0.14 nm for CaFb. These distributions indicate that CaFb and sodium alendronate maintain relatively stable binding poses, whereas calcium alendronate shows larger conformational fluctuations, consistent with its less favorable binding energies. Experimentally, CaFb exhibited the greatest chemisorbed amount and percentage on both HAp and HApTi, followed by sodium and calcium alendronate. HApTi supported higher loadings than HAp for all ligands. Release studies demonstrated a pronounced burst and rapid plateau for both alendronate salts, whereas CaFb displayed a slower initial release followed by a prolonged, quasi-linear liberation over 14 days. Conclusions: The convergence between in silico and adsorption–release data highlights CaFb as the most promising candidate among the tested ligands for long-term functionalization of HAp and HApTi surfaces. Its stronger and more stable binding, higher loading capacity and more sustained release profile suggest that CaFb-coated HApTi implants may provide a favorable basis for future in vitro and in vivo studies aimed at improving osseointegration and mitigating periprosthetic osteolysis, although direct evidence for osteolysis prevention was not obtained in the present work.