Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti-angiogenesis, anti-human immunodeficiency virus (HIV), anti-hepatitis B virus, anti-microbial, anti-inflammatory, and neuro-protective bio-activities. However, the effect of P. cuspidatum extract (PCE) on drug-resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE-treated cisplatin-resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration-and time-dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3-GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4' ,6-diamidino-2-phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) double staining. PCE significantly stimulated caspase-9 and -3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin-1, LC3, Bax and cleaved caspase-3, while it decreased the protein expression of Bcl-2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin-resistant human oral cancer.

Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression. High expression of JMJD5 in oral cancer was significantly associated with tumor size ( P = 0.0241), cervical node metastasis ( P = 0.0001) and clinical stage ( P = 0.0002), was associated with worse survival rate compared with that of the total cohort ( P = 0.0002). Collectively the data indicate that JMJD5 expression may be suitable for detection of unfavorable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. In addition, silibinin inhibits cancer growth in vitro and in PDTX models. Furthermore, metastasis-associated protein 1 (MTA1) could regulate the expression for JMJD5 and had a positive correlation with JMJD5. Moreover, silibinin could downregulate JMJD5 and MTA1 in oral cancer. Present study thus identifies that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. In addition, silibinin is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating JMJD5 in OSCC, through a mechanism likely involving MTA1/JMJD5 axis.

This study designed a biomimetic implant for reducing healing time and achieving early osseointegration to create an active surface. Bone morphogenetic protein-2 (BMP-2) is a strong regulator protein in osteogenic pathways. Due to hardly maintaining BMP-2 biological function and specificity, BMP-2 efficient delivery on implant surfaces is the main challenge for the clinic application. In this study, a novel method for synthesizing functionalized silane film for superior modification with BMP-2 on titanium surfaces is proposed. Three groups were compared with and without BMP-2 on modified titanium surfaces in vitro and in vivo: mechanical grinding; electrochemical modification through potentiostatic anodization (ECH); and sandblasting, alkali heating, and etching (SMART). Cell tests indicated that the ECH and SMART groups with BMP-2 markedly promoted D1 cell activity and differentiation compared with the groups without BMP-2. Moreover, the SMART group with a BMP-2 surface markedly promoted early alkaline phosphatase expression in the D1 cells compared with the other surface groups. Compared with these groups in vivo, SMART silaning with BMP-2 showed superior bone quality and created contact areas between implant and surrounding bones. The SMART group with BMP-2 could promote cell mineralization in vitro and osseointegration in vivo, indicating potential clinical use.

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Finite element analysis (FEA) has always been an important tool in studying the influences of stress and deformation due to various loads on implants to the surrounding jaws. This study assessed the influence of two different types of dental implant model on stress dissipation in adjoining jaws and on the implant itself by utilizing FEA. This analysis aimed to examine the effects of increasing the number of fences along the implant and to compare the resulting stress distribution and deformation with surrounding bones. When a vertical force of 100 N was applied, the largest displacements found in the three-fenced and single-fenced models were 1.7469 and 2.5267, respectively, showing a drop of 30.8623%. The maximum stress found in the three-fenced and one-fenced models was 13.518 and 22.365 MPa, respectively, showing a drop of 39.557%. Moreover, when an oblique force at 35° was applied, a significant increase in deformation and stress was observed. However, the three-fenced model still had less stress and deformation compared with the single-fenced model. The FEA results suggested that as the number of fences increases, the stress dissipation increases, whereas deformation decreases considerably.