Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells.

OBJECTIVE: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. METHODOLOGY: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. RESULTS: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). CONCLUSIONS: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells

Abstract Objective: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. Methodology: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. Results: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). Conclusions: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Elevated red blood cell distribution width predicts poor prognosis in patients with oral squamous cell carcinoma.

INTRODUCTION: Although red blood cell distribution width (RDW) has been reported to reflect inflammation and nutritional status and to predict prognosis in several different types of cancer, little is known about how RDW might be related to oral squamous cell carcinoma (OSCC). The present study aimed to investigate the prognostic value of preoperative RDW in OSCC patients. MATERIALS AND METHODS: We included 236 OSCC patients from Jinan Stomatological Hospital (Shandong, People's Republic of China) in this retrospective study. All enrolled patients were divided into 2 groups: high RDW (≥15%) and low RDW (<15%) according to the detected RDW values. The correlation of RDW and clinical characteristics was explored, and the prognostic significance of RDW evaluated using Kaplan-Meier curves, log-rank analysis, and the Cox proportional hazards model. RESULTS: The pretreatment median RDW among all OSCC patients was 14.4%, with a range from 11.6% to 24.5%. The RDW was found to be significantly correlated with node metastasis, tumor length, and TNM stage (P<0.05 for all). As for biochemical parameters, the results showed that higher RDW values were significantly associated with hemoglobin, mean corpuscular volume, white blood cell count, albumin, and C-reactive protein (P<0.01 for all). A significant association of RDW with the tumor marker cytokeratin 19 fragments (CYFRA21-1) and squamous cell carcinoma antigen (SCC-Ag) was also observed (P=0.02, and P=0.03; respectively). Moreover, patients with higher RDW were more likely to receive postoperative therapy (P=0.02). Kaplan-Meier survival curves showed that a high RDW was significantly associated with poor overall survival (OS) (P<0.01), especially in the early stages (I-II). Multivariate analysis revealed that an elevated RDW at diagnosis was an independent prognostic factor for shorter OS (HR =1.46, 95% CI: 1.13-2.86) after adjustment for other cancer-related prognostic factors. CONCLUSION: These data suggest that an elevated preoperative RDW (≥15%) at diagnosis may independently predict poorer OS in patients with OSCC, but better-designed studies in the future should be performed to further confirm the value of monitoring RDW.

The association between MTHFR gene polymorphisms (C677T, A1298C) and oral squamous cell carcinoma: A systematic review and meta-analysis.

A consensus has not been reached regarding the association of MTHFR gene polymorphism and susceptibility to oral squamous cell carcinoma (OSCC). We performed a meta-analysis to better evaluate the association between MTHFR C677T, A1298C polymorphism and OSCC risk. The studies regarding the association of MTHFR C677T, A1298C polymorphisms and OSCC were identified in PubMed and EMBASE and Google Scholar. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect model. The associations between MTHFR polymorphisms and OSCC risk were assessed under the dominant, recessive and additive models. A collective total of 1539 OSCC patients and 2131 normal controls were included across 13 studies. The minor T allele of MTHFR C677T was significantly associated with the increased risk of OSCC development(OR = 1.35, 95%CI 1.04-1.76). Individuals carrying the ''T" allele (TT+CT) had a nearly 43% increased risk for OSCC development when compared with CC (OR = 1.43, 95%CI 1.02-1.99). Under additive model, the results also showed that individuals with CT or TT genotype were more susceptible to OSCC than CC (OR = 1.45, 95%CI 1.02-2.08; OR = 1.79, 95%CI 1.28-2.50; respectively). The subgroup analysis by ethnicity revealed that significant difference in C677T allele distribution could be observed in European (OR = 1.33, 95%CI 1.02-1.75) rather than Asian (OR = 1.59, 95%CI 0.91-2.78). No significant association of MTHFR A1298C polymorphism and OSCC risk could be observed. The present study revealed that T allele and TT genotype of MTHFR C677T polymorphism were significantly associated with the increased risk of OSCC development.