Staphylococcus aureus enhances osteoclast differentiation and bone resorption by stimulating the NLRP3 inflammasome pathway.

BACKGROUND: Osteomyelitis is one of the most challenging infectious diseases and is mainly caused by Staphylococcus aureus (S. aureus). In this study, we analyzed the effect of S. aureus on osteoclast differentiation and its possible molecular mechanism. METHODS: We cultured RAW 264.7 cells with live S. aureus for 5 days. We assessed cell viability and the formation of resorption pits. We tested the NLRP3 inflammasome signaling pathways and measured the mRNA expression levels of osteoclastspecific genes, including TRAP, MMP9, cathepsin K, calcitonin receptor and ATP6V0d2. Furthermore, we analyzed the protein expression levels of the protein in the NF-κB and p38 MAPK signaling pathways to clarify the signaling pathways by which S. aureus promotes osteoclast differentiation. RESULTS: Staphylococcus aureus induced NLRP3 inflammasome activation. S. aureus promoted bone resorption and enhanced the expression of osteoclastspecific genes, such as TRAP, MMP9, cathepsin K, calcitonin receptor and ATP6V0d2. MCC950 was used to inhibit NLRP3 inflammasome activity. Osteoclast differentiation and the expression of osteoclastspecific genes induced by S. aureus were inhibited by MCC950 pretreatment. The degradation of IκBα and phosphorylation of P65 were increased under the induction of S. aureus, but proteins in the p38 MAPK signaling pathway did not change significantly. CONCLUSION: Staphylococcus aureus induces osteoclast differentiation and promotes bone resorption in vitro, and the NLRP3 inflammasome signaling pathway plays a significant role in this process. S. aureus-induced NLRP3 inflammasome activation was mainly dependent on the NF-κB signaling pathway during osteoclastogenesis.

Combination of neutrophil/lymphocyte ratio and albumin/bilirubin grade as a prognostic predictor for hepatocellular carcinoma patients undergoing curative hepatectomy.

BACKGROUND AND AIM: Prognosis determination is essential for hepatocellular carcinoma (HCC) patient management and treatment planning. The current study aimed to evaluate the prognosis performance of NLR, ALBI, and the combination of NLR-ALBI in determining the overall survival (OS) of HCC patients under curative hepatectomy. METHODS: 144 primary HCC patients with curative hepatectomy were recruited in the retrospective study. The clinicopathologic characteristics and OS were compared between stratified groups. The predictive performance of NLR, ALBI, and the combination of NLR-ALBI was explored by the area under the receiver operating characteristic curve (AUC). Univariate and multivariate analyses were used to determine the risk factors of OS. RESULTS: AUC determined NLR cutoff > 2.60 for predicting prognosis. The univariate analysis indicated pathological differentiation, tumor size, AFP, TNM stage, NLR score, and ALBI grade were significant indicators of OS. However, only TMN grade, AFP, NLR score, and NLR-ALBI score were identified as independent predictors of OS in the multivariable analysis. The AUC of NLR, ALBI and the combination of NLR-ALBI was 0.618(95%CI 0.56-0.710), 0.533 (95%CI 0.437-0.629), 0.679 (95%CI 0.592-0.767) respectively. Patients with higher NLR-ALBI scores presented worse outcomes than those with lower NLR-ALBI scores. CONCLUSION: NLR is an independent prognostic factor of HCC and a reliable biomarker in predicting the OS of HCC patients. The combination of NLR-ALBI showed a better prognostic performance than using NLR or ALBI alone, implicating the effectiveness and feasibility of combining multiple risk factors for postoperative prognosis assessment.