Tissue inflammation is an important problem in the field of human adipose-derived stem cell (ASC)-based therapeutic bone regeneration. Many studies indicate that inflammatory cytokines are disadvantageous for osteogenic differentiation and bone formation. Therefore, overcoming inflammation would be greatly beneficial in promoting ASC-mediated bone regeneration. The present study aims to investigate the potential anti-inflammatory role of Prostaglandin G/H synthase 1 (PTGS1) during the osteogenic differentiation of ASCs. We performed TNFα treatment to investigate the response of PTGS1 to inflammation. Loss- and gain-of-function experiments were applied to investigate the function of PTGS1 in the osteogenic differentiation of ASCs ex vivo and in vivo. Western blot and confocal analyses were used to determine the molecular mechanism of PTGS1-regulated osteogenic differentiation. Our work demonstrates that PTGS1 expression is significantly increased upon inflammatory cytokine treatment. Both ex vivo and in vivo studies indicate that PTGS1 is required for the osteogenic differentiation of ASCs. Mechanistically, we show that PTGS1 regulates osteogenesis of ASCs via modulating the NF-κB signaling pathway. Collectively, this work confirms that the PTGS1-NF-κB signaling pathway is a novel molecular target for ASC-mediated regenerative medicine.

Twist1 confers multidrug resistance in colon cancer through upregulation of ATP-binding cassette transporters Twist1 confers multidrug resistance in colon cancer through upregulation of ATP-binding cassette transporters

The E3 ubiquitin ligase complex CDC20-activated anaphase-promoting complex/Cyclosome (APC/C ^CDC20 ) plays a critical role in governing mitotic progression by targeting key cell cycle regulators for degradation. Cell division cycle protein 20 homolog (CDC20), the co-activator of APC/C, is required for full ubiquitin ligase activity. In addition to its well-known cell cycle-related functions, we demonstrate that CDC20 plays an essential role in osteogenic commitment of bone marrow mesenchymal stromal/stem cells (BMSCs). Cdc20 conditional knockout mice exhibit decreased bone formation and impaired bone regeneration after injury. Mechanistically, we discovered a functional interaction between the WD40 domain of CDC20 and the DNA-binding domain of p65. Moreover, CDC20 promotes the ubiquitination and degradation of p65 in an APC11-dependent manner. More importantly, knockdown of p65 rescues the bone loss in Cdc20 conditional knockout mice. Our current work reveals a cell cycle-independent function of CDC20, establishes APC11 ^CDC20 as a pivotal regulator for bone formation by governing the ubiquitination and degradation of p65, and may pave the way for treatment of bone-related diseases.

Mouthguards are proven devices placed inside the mouth to prevent oral lacerations, dental injuries, and jaw fractures. Endorsed by the World Dental Federation, mouthguards are crucial for preventing orofacial and dental trauma. However, their adoption in sports is challenged by limited guidance, communication barriers, and cost considerations. Based on extensive literature research in PubMed/MEDLINE, this narrative review summarizes the historical development of mouthguards, elaborates on their primary classifications, and examines the factors influencing their properties. Importantly, the impact of mouthguards on sports performance is clarified in this study. Overall, using mouthguards in sports not only reduces the occurrence and severity of dental injuries but also holds promise for enhancing athletic performances such as strength, aerobic capacity, agility, balance, and flexibility. Therefore, promoting mouthguard use in the sports community should be encouraged.