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Background: Chemokine receptors have a crucial role in regulating tumor mediating immunity and are also implicated in the prognosis of some cancers. Here, the association between CXC chemokine receptors (CXCR2–5) and prognosis in osteosarcoma was studied.Methods: Differences between CXCR2, CXCR3, CXCR4, and CXCR5 expression and overall survival (OS) and event-free survival (EFS) were compared using Kaplan–Meier analyses. The associations of CXCR3 expression with clinical features and the prognosis were also analyzed. The signaling pathways modulated by CXCR3 were investigated. The correlations between CXCR3 and immune infiltrates were investigated.Results: The expression of CXCR2, CXCR4, and CXCR5 was not associated with the prognosis, but CXCR3 low expression was correlated with worse OS and EFS of osteosarcoma, especially for female, patients aged less than 15.1 years, or patients without metastasis. Low CXCR3 expression was related to tumor site and histologic response (P<0.05), but not associated with other clinical characteristics. Multivariate Cox analysis revealed that CXCR3 remained independently associated with the prognosis, especially for OS (hazard ratio (HR) = 3.26, 95% CI = 1.15–9.24, P=0.026). The cell adhesion, apoptosis, metabolism, KRAS, P53, NOTCH, reactive oxygen species (ROS), PI3K/Akt/mTOR, vascular endothelial growth factor (VEGF), inflammation, and immune-related pathways such as IL-6/JAK/STAT3, TNF-α via NF-κB, Toll/NOD-like receptor, and complement were modulated by CXCR3. CXCR3 expression showed an especially positive correlation with immune infiltration of T cells CD8, macrophages M1, plasma cells, and NK cells activated.Conclusions: CXCR3 may be an independent risk factor for the prognosis and is most likely to benefit from immunotherapy in osteosarcoma.

Background Osteosarcoma is a primary bone aggressive cancer, affecting adolescents worldwide. Increasing evidence suggests that dysfunction of microRNAs (miRNAs) plays a pivotal role in malignancies. The aim of this study was to evaluate the potential functions of miR-181c and verifying its regulatory effects on SMAD7 in osteosarcoma. Material/Methods The expressions of miR-181c and SMAD7 in osteosarcoma were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, invasion and migration abilities were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Transwell assay. Bioinformatics analysis and luciferase reporter assay were used to explore the interaction between miR-181c and SMAD7. Western blot was performed to determine the functions of miR-181c on osteosarcoma cell epithelial-to-mesenchymal transition (EMT) and transforming growth factor-β (TGF-β) signaling pathway. Results Decreased expression levels of miR-181c and SMAD7 were identified in osteosarcoma using qRT-PCR. The downregulated miR-181c and SMAD7 expressions indicated poor prognosis of osteosarcoma patients. Moreover, miR-181c overexpression prominently repressed osteosarcoma cell proliferation, invasion, and migration abilities via modulating EMT and TGF-β signaling pathway. SMAD7 functioned as an important target for miR-181c in osteosarcoma cells. Furthermore, upregulation of miR-181c dramatically suppressed osteosarcoma tumorigenesis in vivo. Conclusions These findings indicated that miR-181c suppressed osteosarcoma progression, providing new insight into the pathogenesis and representing a potential therapeutic target for osteosarcoma.

This study investigates the hepatoprotective effect of the aqueous extract of Polygonatum sibiricum (AEPS) against ethanol-induced oxidative stress and explores underlying mechanisms. AEPS was administered by gavage to ICR mice for 30 days. The experimental mice were fed a 5% (v/v) ethanol on last 10 days and followed by a single megadose of ethanol (5 g/kg) to induce ethanol-induced liver injury. Pretreatment with AEPS significantly suppressed the ethanol-induced elevation of aminotransferase activities, total bilirubin (TBIL) level, triglyceride level, and alleviated liver histopathological lesions. Meanwhile, AEPS reduced the level of oxidative stress in the liver and significantly suppressed the mRNA levels of NOX1, p67phox, gp91phox, and CYP2E1. Additionally, AEPS significantly increased the mRNA and protein levels of Nrf2 and its downstream antioxidant genes and promoted the nuclear translocation of Nrf2 in mice liver. Therefore, AEPS can effectively reduce ethanol-induced liver injury via regulation of the Nrf2/ARE pathway. Practical applications Alcohol abuse and alcoholism have become a serious public health problem worldwide. Since liver is the major organ of alcohol metabolism, the most impactful damage of alcohol occurs in the liver. Polygonatum sibiricum is a traditional Chinese galenical and it also can be used as food ingredients. Most studies have reported that polysaccharide, flavonoids and saponins are the main bioactive compounds in Polygonatum sibiricum which play important roles in anti-oxidation. AEPS is the aqueous extract of Polygonatum sibiricum and AEPS can protect the mice liver against ethanol-induced oxidative damage. Thus it can be potential antioxidants to product hepatoprotective food and the study also provides a theoretical basis for the development and application of food about Polygonatum sibiricum.

Background:Neoadjuvant chemotherapy for patients with high-grade osteosarcoma has highly improved the clinical survival. However, the prognostic and predictive role of P16 expression after neoadjuvant chemotherapy remains unclear. We first determined whether P16 expression can become a potential prognostic and predictive biomarker in high-grade osteosarcoma.Methods:This meta-analysis was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. Eligible studies were pooled and the overall odds ratios (ORs) and hazard ratios (HRs) with the corresponding 95% confidence intervals (95% CIs) were calculated in this analysis.Results:Four studies involving a total of 527 patients with high-grade osteosarcoma receiving neoadjuvant chemotherapy were identified. We did not find that P16 expression was correlated with sex status, histologic subtype, and tumor site (P > .1). P16 expression was found to be significantly associated with a “good” response to neoadjuvant chemotherapy (OR = 4.69, P < .001). A significant relationship was observed between p16 expression and pathologic complete response after neoadjuvant chemotherapy using multivariate analysis (OR = 9.63, P = .001). The expression of the P16 was not associated with clinical outcomes in overall survival (OS) and disease-free survival (DFS) by multivariate analysis (OS: P = .448; DFS: P = .263).Conclusions:The use of P16 expression could become a promising predictive biomarker of the response to neoadjuvant chemotherapy in the white population with high-grade osteosarcoma. However, it was not correlated with the prognosis of patients in OS and DFS. More clinical researches are very essential in Asians in the future.