Intracellular NO-Releasing Hyaluronic Acid-Based Nanocarriers: A Potential Chemosensitizing Agent for Cancer Chemotherapy.

In this work, we investigate whether S-nitrosoglutathione (GSNO)-conjugated hyaluronic acid-based self-assembled nanoparticles (GSNO-HANPs) can be useful as a chemosensitizing agent to improve the anticancer activity of doxorubicin (DOX). The GSNO-HANPs were prepared by aqueous assembly of GSNO-conjugated HA with grafted poly(lactide- co-glycolide). Aqueous GSNO stability shielded within the assembled environments of the GSNO-HANPs was greatly enhanced, compared to that of free GSNO. The NO release from the GSNO-HANPs was facilitated in the presence of hyaluronidase-1 (Hyal-1) and ascorbic acid at intracellular concentrations. Microscopic analysis showed GSNO-HANPs effectively generated NO within the cells. We observed that NO made the human MCF-7 breast cancer cells vulnerable to DOX. This chemosensitizing activity was supported by the observation of an increased level of ONOO- (peroxynitrite), a highly reactive oxygen species, upon co-treatment with the GSNO-HANPs and DOX. Apoptosis assays showed that GSNO-HANP alone exhibited negligible cytotoxic effects and reinforced apoptotic activity of DOX. Animal experiments demonstrated the effective accumulation of GSNO-HANPs in solid MCF-7 tumors and effectively suppressed tumor growth in combination with DOX. This hyaluronic acid-based intracellularly NO-releasing nanoparticles may serve as a significant chemosensitizing agent in treatments of various cancers.

Characteristics of Mesiodens and Its Related Complications.

PURPOSE: The purpose of this study was to evaluate the effect of mesiodens on adjacent permanent anterior teeth according to mesiodens characteristics. METHODS: To evaluate complications associated with mesiodens, according to its characteristics, a total of 107 children were studied who had a chief complaint of mesiodens. The number, morphology, direction of eruption, position of mesiodens, root developmental stage and complications related to adjacent permanent maxillary central incisors (APMCIs) were evaluated by radiographic imaging. RESULTS: The final sample was 107 children and total number of mesiodens was 153. Among these patients, 67 percent showed clinical complications. The primary morphologic type was conical (96.1 percent) and the most common direction of eruption was inverted (56.2 percent). Most mesiodens (80.4 percent) were located on the palatal side of the APMCIs. CONCLUSIONS: The direction of mesiodens and the eruption period of adjacent permanent incisors affected the complication rate. The positional relationship between mesiodens and adjacent permanent central incisors had the strongest influence on both eruption disturbance and displacement of permanent central incisors.

Correlation between clinical clerkship achievement and objective structured clinical examination (OSCE) scores of graduating dental students on conservative dentistry.

OBJECTIVES: This study aimed to investigate the effect of clinical clerkship-associated achievements, such as performance of procedures at the student clinic, observation, and attitude towards a clerkship, on the objective structured clinical examination (OSCE) scores of dental students graduating in restorative dentistry. MATERIALS AND METHODS: The OSCEs consisted of two stations designed to assess students' clinical skills regarding cavity preparation for a class II gold inlay and a class IV composite restoration. The clerkship achievements, consisting of the number of student clinical procedures performed, observation-related OSCE, and scores of their attitudes towards a conservative dentistry clerkship, were assessed. Correlation and multiple regression analyses were conducted. RESULTS: The correlation coefficient between the OSCE scores for cavity preparation for a class II gold restoration and clerkship attitude scores was 0.241 (p < 0.05). Regarding a class IV composite restoration, OSCE scores showed statistically significant correlations with the observation (r = 0.344, p < 0.01) and attitude (r = 0.303, p < 0.01) scores. In a multiple regression analysis, attitudes towards a clerkship (p = 0.033) was associated with the cavity preparation for a class II gold inlay OSCE scores, while the number of procedure observations (p = 0.002) was associated with the class IV composite restoration OSCE scores. CONCLUSIONS: The number of clinical procedures performed by students, which is an important requirement for graduation, showed no correlation with either of the OSCEs scores.

Porphyromonas gingivalis lipopolysaccharide regulates interleukin (IL)-17 and IL-23 expression via SIRT1 modulation in human periodontal ligament cells.

Increased interleukin (IL)-17 and IL-23 levels exist in the gingival tissue of periodontitis patients, but the precise molecular mechanisms that regulate IL-17 and IL-23 production remain unknown. The aim of this study was to explore the role of SIRT1 signaling on Porphyromonas gingivalis lipopolysaccharide (LPS)-induced IL-17 and IL-23 production in human periodontal ligament cells (hPDLCs). IL-17 and IL-23 production was significantly increased in LPS-treated cells. LPS treatment also led to the upregulation of SIRT1 mRNA and protein expression. LPS-induced IL-17 and IL-23 upregulation was attenuated by pretreatment with inhibitors of phosphoinositide 3-kinase (PI3K), p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and NF-κB, as well as neutralizing antibodies against Toll-like receptors (TLRs) 2 and 4. Sirtinol treatment (a known SIRT1 inhibitor) or SIRT1 knockdown by small interfering RNA blocked LPS-stimulated IL-17 and IL-23 expression. Further investigation showed that LPS decreased osteoblast markers (i.e., ALP, OPN, and BSP) and concomitantly increased osteoclast markers (i.e., RANKL and M-CSF). This response was attenuated by inhibitors of the PI3K, p38, ERK, JNK, NF-κB, and SIRT1 pathways. These findings, for the first time, suggest that human periodontopathogen P. gingivalis LPS is implicated in periodontal disease bone destruction and may mediate IL-17 and IL-23 release from hPDLCs. This process is dependent, at least in part, on SIRT1-Akt/PI3K-MAPK-NF-κB signaling.