Physicochemical, Biological, and Antibacterial Properties of Four Bioactive Calcium Silicate-Based Cements.

Calcium silicate-based cement (CSC) is a pharmaceutical agent that is widely used in dentistry. This bioactive material is used for vital pulp treatment due to its excellent biocompatibility, sealing ability, and antibacterial activity. Its drawbacks include a long setting time and poor maneuverability. Hence, the clinical properties of CSC have recently been improved to decrease its setting time. Despite the widespread clinical usage of CSC, there is no research comparing recently developed CSCs. Therefore, the purpose of this study is to compare the physicochemical, biological, and antibacterial properties of four commercial CSCs: two powder-liquid mix types (RetroMTA® [RETM]; Endocem® MTA Zr [ECZR]) and two premixed types (Well-Root™ PT [WRPT]; Endocem® MTA premixed [ECPR]). Each sample was prepared using circular Teflon molds, and tests were conducted after 24 h of setting. The premixed CSCs exhibited a more uniform and less rough surface, higher flowability, and lower film thickness than the powder-liquid mix CSCs. In the pH test, all CSCs showed values between 11.5 and 12.5. In the biological test, cells exposed to ECZR at a concentration of 25% showed greater cell viability, but none of the samples showed a significant difference at low concentration (p > 0.05). Alkaline phosphatase staining revealed that cells exposed to ECZR underwent more odontoblast differentiation than the cells exposed to the other materials; however, no significant difference was observed at a concentration of 12.5% (p > 0.05). In the antibacterial test, the premixed CSCs showed better results than the powder-liquid mix CSCs, and ECPR yielded the best results, followed by WRPT. In conclusion, the premixed CSCs showed improved physical properties, and of the premixed types, ECPR exhibited the highest antibacterial properties. For biological properties, none of these materials showed significant differences at 12.5% dilution. Therefore, ECPR may be a promising material with high antibacterial activity among the four CSCs, but further investigation is needed for clinical situations.

Physicochemical, Pre-Clinical, and Biological Evaluation of Viscosity Optimized Sodium Iodide-Incorporated Paste.

This study aimed to investigate the impact of different viscosities of silicone oil on the physicochemical, pre-clinical usability, and biological properties of a sodium iodide paste. Six different paste groups were created by mixing therapeutic molecules, sodium iodide (D30) and iodoform (I30), with calcium hydroxide and one of the three different viscosities of silicone oil (high (H), medium (M), and low (L)). The study evaluated the performance of these groups, including I30H, I30M, I30L, D30H, D30M, and D30L, using multiple parameters such as flow, film thickness, pH, viscosity, and injectability, with statistical analysis (p < 0.05). Remarkably, the D30L group demonstrated superior outcomes compared to the conventional iodoform counterpart, including a significant reduction in osteoclast formation, as examined through TRAP, c-FOS, NFATc1, and Cathepsin K (p < 0.05). Additionally, mRNA sequencing showed that the I30L group exhibited increased expression of inflammatory genes with upregulated cytokines compared to the D30L group. These findings suggest that the optimized viscosity of the sodium iodide paste (D30L) may lead to clinically favorable outcomes, such as slower root resorption, when used in primary teeth. Overall, the results of this study suggest that the D30L group shows the most satisfactory outcomes, which may be a promising root-filling material that could replace conventional iodoform-based pastes.

Comparative Study of Esophageal Self-expandable Metallic Stent Insertion and Gastrostomy Feeding for Dysphagia Caused by Lung Cancer.

Background/Aims: Dysphagia is encountered in a large proportion of patients with lung cancer and is associated with malnutrition and a poor quality of life. This study compared the clinical outcomes of self-expandable metallic stent (SEMS) insertion and percutaneous gastrostomy (PG) feeding for patients with lung cancer and dysphagia. Methods: A total of 261 patients with lung cancer, who underwent either SEMS insertion (stent group) or PG (gastrostomy group) as an initial treatment procedure for dysphagia between July 1997 and July 2015 at the Samsung Medical Center, were reviewed retrospectively, and 84 patients with esophageal obstruction were identified. The clinical outcomes, including the overall survival, additional intervention, complications, and post-procedural nutritional status in the two groups, were compared. Results: Among the 84 patients finally analyzed, 68 patients received SEMS insertion and 16 had PG. The stent group had less cervical obstruction and more mid-esophageal obstruction than the gastrostomy group. The Kaplan-Meier curves revealed similar overall survival in the two groups. Multivariate analysis showed that the two modalities had similar survival rates (PG compared with SEMS insertion, hazard ratio 0.682, p=0.219). Fifteen patients (22.1%) in the stent group received additional intervention, whereas there was no case in the gastrostomy group (p=0.063). The decrease in the serum albumin level after the procedure was lower in the gastrostomy group than in the stent group (-0.20±0.54 g/dL vs. -0.65±0.57 g/dL, p=0.013). Conclusions: SEMS insertion and PG feeding for relieving dysphagia by lung cancer had a comparable survival outcome. On the other hand, PG was associated with a better nutritional status.

Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization.

PURPOSE: To investigate the effects of resveratrol on the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE-19) cells, and on experimental choroidal neovascularization (CNV) in mice. MATERIALS AND METHODS: ARPE-19 cells were treated with different concentrations of resveratrol and then incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1α, and expression of VEGF. The effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1α were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4. RESULTS: In ARPE-19 cells, resveratrol significantly inhibited HIF-1α and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1α degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner. CONCLUSION: Resveratrol may have therapeutic value in the management of diseases involving pathological neovascularization.

Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery.

Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N=432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N=186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N=216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N=300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N=216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence=3.16, p=0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio=1.77, p=0.0053).

Effect of amiloride to retinal toxicity induced by tissue plasminogen activator.

PURPOSE: The effects of amiloride on cellular toxicity caused by tissue plasminogen activator (tPA) in mouse primary retinal cells were investigated. METHODS: Primary retinal cell cultures were maintained using glial conditioned medium. Commercial tPA and L-arginine were added, and the level of cyclic guanosine monophosphate (cyclic-GMP) in the culture supernatant was assessed using an ELISA assay. We measured the cell viability of cultured retinal cells pretreated with three different concentrations of amiloride (1, 10, and 100 µm) in addition to commercial tPA or L-arginine treatment. RESULTS: After exposing the cultured mouse retinal cells to tPA plus L-arginine or L-arginine alone, cyclic-GMP concentrations were 61.9 ± 5.1 pmole/mL and 63.1 ± 6.1 pmole/mL, respectively. However, the control group had a significantly lower concentration of cyclic-GMP (37.2 ± 3.4 pmole/mL, p < 0.01). The cyclic GMP-dissolved solution did not cause retinal cell death. In the control group and the group treated with 1 µm amiloride and tPA containing L-arginine, the cell viability was 43.7% and 44.5%, respectively. However, cell viability increased to 70.6% with 10 µm amiloride and 78.4% with 100 µm amiloride (p = 0.015). CONCLUSIONS: L-arginine increases intracellular cyclic-GMP and may give rise to retinal cells through this mechanism. In addition, amiloride in concentrations greater than 10 µm protects against L-arginine-induced retinal cell death.

Cellular proliferative effect of dexamethasone in immortalized trabecular meshwork cell (TM5) line.

Dexamethasone (DEX), one of the corticosteroid hormones, is one of the most common therapeutic strategies in ophthalmological treatment. Despite its widespread use and clinical efficiency, little is known regarding the specific effects of DEX on cell growth, differentiation and cell death in human trabecular meshwork cells. The presence of the glucocorticoid receptor (GR, dexamethasone receptor) in TM-5 cell line, which was derived from the primary human trabecular meshwork cells, was verified by RT-PCR and western blot analysis. The effects of DEX on the cellular proliferation of TM5 cells were measured by a BrdU incorporation assay. Western blot analysis were used to examine the effects of DEX on the Ras/MEK/ERK signaling pathway. The total Ras, MEK1/2 and ERK1/2 protein levels as well as the levels of activated (phosphorylated) form were both significantly increased by the DEX treatment for 5 days. Both MEK1/2 and ERK1/2 were significantly activated by phosphorylation after 10 minutes. The dependence of this increased cell proliferation on GR activation by DEX and the sustained activation of ERK was examined using RU486 (a GR inhibitor) and U0126 (a MEK inhibitor). Both RU486 and U0126 prevented the induction of cell proliferation by the DEX treatment in the TM5 cells. In conclusion this study demonstrated that GR is expressed in TM5 cells. Secondly, DEX treatment for 5 days stimulates cell proliferation in TM5 cells, and that this increased proliferation effect is mediated by the Ras/MEK/ERK pathway.