Roles of prostaglandins in immunosuppression.

Prostaglandins (PGs) play a crucial and multifaceted role in various physiological processes such as intercellular signaling, inflammation regulation, neurotransmission, vasodilation, vasoconstriction, and reproductive functions. The diversity and biological significance of these effects are contingent upon the specific types or subtypes of PGs, with each PG playing a crucial role in distinct physiological and pathological processes. Particularly within the immune system, PGs are essential in modulating the function of immune cells and the magnitude and orientation of immune responses. Hence, a comprehensive comprehension of the functions PG signaling pathways in immunosuppressive regulation holds substantial clinical relevance for disease prevention and treatment strategies. The manuscript provides a review of recent developments in PG signaling in immunosuppressive regulation. Furthermore, the potential clinical applications of PGs in immunosuppression are also discussed. While research into the immunosuppressive effects of PGs required further exploration, targeted therapies against their immunosuppressive pathways might open new avenues for disease prevention and treatment.

METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner to promote osteosarcoma progression.

N6-methyladenosine (m6A) is the most abundant and well-studied internal modification of messenger RNAs (mRNAs). Although m6A mRNA modification has been frequently observed in osteosarcoma, the roles and underlying mechanisms of m6A modification are not yet fully elucidated. In this study, an m6A regulator, METTL3, showed to be dramatically up-regulated within osteosarcoma tissues and cells than non-cancerous healthy samples and human normal osteoblasts, respectively. In vitro, knockdown of METTL3 suppressed the viability of osteosarcomas, and their abilities to migrate and invade; in vivo, knockdown of METTL3 repressed tumor growth within xenotransplant tumor model. METTL3 upregulates COPS5 expression may be through promoting COPS5 methylation to stabilize COPS5 mRNA. The expression level of COPS5 also showed to be up-regulated within osteosarcoma tissue samples and cells. COPS5 knockdown caused no changes in METTL3 effects on METTL3 expression but partially eliminated METTL3 effects on COPS5 expression. METTL3 overexpression promoted, whereas COPS5 knockdown inhibited the malignant behaviors of osteosarcoma cells; COPS5 knockdown partially eliminated the effects of METTL3 overexpression on osteosarcoma cells. Conclusively, METTL3 and COPS5 serve as oncogenic regulators in osteosarcoma. METTL3 upregulates COPS5 expression in osteosarcoma in an m6A-related manner.

Biofunctionalization of 3D Printed Porous Tantalum Using a Vancomycin-Carboxymethyl Chitosan Composite Coating to Improve Osteogenesis and Antibiofilm Properties.

3D-printed porous tantalum scaffold has been increasingly used in arthroplasty due to its bone-matching elastic modulus and good osteoinductive ability. However, the lack of antibacterial ability makes it difficult for tantalum to prevent the occurrence and development of periprosthetic joint infection. The difficulty and high cost of curing periprosthetic joint infection (PJI) and revision surgery limit the further clinical application of tantalum. Therefore, we fabricated vancomycin-loaded porous tantalum scaffolds by combining the chemical grafting of (3-aminopropyl)triethoxysilane (APTES) and the electrostatic assembly of carboxymethyl chitosan and vancomycin for the first time. Our in vitro experiments show that the scaffold achieves rapid killing of initially adherent bacteria and effectively prevents biofilm formation. In addition, our modification preserves the original excellent structure and biocompatibility of porous tantalum and promotes the generation of mineralized matrix and osteogenesis-related gene expression by mesenchymal stem cells on the surface of scaffolds. Through a rat subcutaneous infection model, the composite bioscaffold shows efficient bacterial clearance and inflammation control in soft tissue and creates an immune microenvironment suitable for tissue repair at an early stage. Combined with the economic friendliness and practicality of its preparation, this scaffold has great clinical application potential in the treatment of periprosthetic joint infection.