Phage Therapy for Bone and Joint Infections: A Comprehensive Exploration of Challenges, Dynamics, and Therapeutic Prospects.

Bone and joint infections (BJI) pose formidable challenges in orthopedics due to antibiotic resistance and the complexities of biofilm, complicating treatment. This comprehensive exploration addresses the intricate challenges posed by BJI and highlights the significant role of phage therapy as a non-antibiotic strategy. BJI, which encompass prosthetic joint infections, osteomyelitis, and purulent arthritis, are exacerbated by biofilm formation on bone and implant surfaces, hindering treatment efficacy. Gram-negative bacterial infections, characterized by elevated antibiotic resistance, further contribute to the clinical challenge. Amidst this therapeutic challenge, phage therapy emerges as a potential strategy, showing unique characteristics such as strict host specificity and biofilm disruption capabilities. The review unveils the dynamics of phages, including their origins, lifecycle outcomes, and genomic characteristics. Animal studies, in vitro investigations, and clinical research provide compelling evidence of the efficacy of phages in treating Staphylococcus aureus infections, particularly in osteomyelitis cases. Phage lysins exhibit biofilm-disrupting capabilities, offering a meaningful method for addressing BJI. Recent statistical analyses reveal high clinical relief rates and a favorable safety profile for phage therapy. Despite its promise, phage therapy encounters limitations, including a narrow host range and potential immunogenicity. The comprehensive analysis navigates these challenges and charts the future of phage therapy, emphasizing standardization, pharmacokinetics, and global collaboration. Anticipated strides in phage engineering and combination therapy hold promise for combating antibiotic-resistant BJI.

Mechanistic elucidation of ferroptosis and ferritinophagy: implications for advancing our understanding of arthritis.

In recent years, the emerging phenomenon of ferroptosis has garnered significant attention as a distinctive mode of programmed cell death. Distinguished by its reliance on iron and dependence on reactive oxygen species (ROS), ferroptosis has emerged as a subject of extensive investigation. Mechanistically, this intricate process involves perturbations in iron homeostasis, dampening of system Xc-activity, morphological dynamics within mitochondria, and the onset of lipid peroxidation. Additionally, the concomitant phenomenon of ferritinophagy, the autophagic degradation of ferritin, assumes a pivotal role by facilitating the liberation of iron ions from ferritin, thereby advancing the progression of ferroptosis. This discussion thoroughly examines the detailed cell structures and basic processes behind ferroptosis and ferritinophagy. Moreover, it scrutinizes the intricate web of regulators that orchestrate these processes and examines their intricate interplay within the context of joint disorders. Against the backdrop of an annual increase in cases of osteoarthritis, rheumatoid arthritis, and gout, these narrative sheds light on the intriguing crossroads of pathophysiology by dissecting the intricate interrelationships between joint diseases, ferroptosis, and ferritinophagy. The newfound insights contribute fresh perspectives and promising therapeutic avenues, potentially revolutionizing the landscape of joint disease management.