Ubiquitination in osteosarcoma:unveiling the impact on cell biology and therapeutic strategies

Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.

Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3inflammasome activation in LPS-induced vascular injury

The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide(2 μg/mL) and administrated by 0.1–2 mmol/L aspirin. The wild type mice were stimulated with LPS(100 μg/kg/day), and 1 h later treated with aspirin(12.5, 62.5, or125 mg/kg/day) and dexamethasone(0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in vitro in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of theendothelial tight junction protein zonula occludens-1/2(ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.