Effect of dentin desensitizers on resin cement bond strengths

Introduction: The crown preparation promotes the exposure of dentin tubules. Thus, to avoid post-operative sensitivity, the first approach involves the use of dentin adhesives, and the second one the use of dentin desensitizers. Objective: This study evaluated the effect of dentin desensitizers on microtensile bond strengths (µTBSs) of a resin cement to dentin. Material and methods: Twenty bovine teeth were prepared until obtaining flat dentin surfaces. A standardized smear layer was created (#600-grit SiC paper). The samples were randomly divided into the following four groups (n = 5): no treatment (Control), treatment with Gluma Desensitizer (Heraeus Kulzer), Super Seal (Phoenix Dental) and Teethmate Desensitizer (Kuraray Noritake Dental). The dentin surfaces were then treated with ED Primer II (Kuraray Noritake Dental). Twenty composite blocks, 4 mm thick (Estenia C&B, Kuraray Noritake Dental) were used. The composite surfaces were abraded with aluminum oxide (50 µm), and then silanized. The composite block was bonded to the dentin surface with a resin cement (Panavia F 2.0, Kuraray Noritake Dental) according to he manufacturer’s instructions. After 24-hour storage (37ºC, 100% RH), the bonded samples were cut into beam–shaped microtensile specimens and loaded in tension until failure. Data were analyzed with one-way ANOVA and the Dunnett’s test (α = 0.05). An SEM was used to examine the failure modes. Results: The µTBSs (MPa ± SD) were: 24.4 ± 3.2 (Control), 14.0 ± 5.6 (Gluma Desensitizer), 8.6 ± 4.7 (Super Seal), and 34.7 ± 4.6 (Teethmate Desensitizer), in which there were significant differences among the four groups (p < 0.05). The Teethmate Desensitizer group showed the highest µTBS, while the Super Seal group showed the lowest mean of µTBS to dentin. Conclusion: The efficacy of the desensitizers is material-dependent; Gluma Desensitizer and Super Seal decreased the µTBSs, however, Teethmate Desensitizer improved it

Update on Enamel Bonding Strategies

Optimal strategies for the application of an adhesive differ between enamel and dentin because of the differences in their composition. The development of adhesive systems has mainly focused on the bonding of dentin, rather than on the enamel, by etching with phosphoric acid (PA). Dental adhesive technologies continue to rapidly advance, and various adhesive systems have been developed since the study of Buonocore in 1955. He introduced the enamel acid-etch technique. Then, the etch-and-rinse (ER) system was developed, and subsequently, the self-etch (SE) system. Universal adhesives are a new generation of one-bottle SE adhesives that can be applied with either ER mode or SE mode, or a combined system involving selective enamel etching mode. Since the combination of PA etching and the SE system differs from conventional ER systems, the enamel bonding strategy should be carefully considered. This concise review of the literature on reliable enamel bonding strategies should prove helpful to clinicians to choose an appropriate adhesive system to achieve optimal clinical outcomes

Synthesis and biological activity of artificial mRNA prepared with novel phosphorylating reagents

Though medicines that target mRNA are under active investigation, there has been little or no effort to develop mRNA itself as a medicine. Here, we report the synthesis of a 130-nt mRNA sequence encoding a 33-amino-acid peptide that includes the sequence of glucagon-like peptide-1, a peptide that stimulates glucose-dependent insulin secretion from the pancreas. The synthesis method used, which had previously been developed in our laboratory, was based on the use of 2-cyanoethoxymethyl as the 2′-hydroxy protecting group. We also developed novel, highly reactive phosphotriester pyrophosphorylating reagents to pyrophosphorylate the 5′-end of the 130-mer RNA in preparation for capping. We completed the synthesis of the artificial mRNA by the enzymatic addition of a 5′-cap and a 3′-poly(A) tail to the pyrophosphorylated 130-mer and showed that the resulting mRNA supported protein synthesis in a cell-free system and in whole cells. As far as we know, this is the first time that mRNA has been prepared from a chemically synthesized RNA sequence. As well as providing a research tool for the intracellular expression of peptides, the technology described here may be used for the production of mRNA for medical applications

Prospective study of daily low-dose nedaplatin and continuous 5-fluorouracil infusion combined with radiation for the treatment of esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Protracted low-dose concurrent chemotherapy combined with radiation has been proposed for enhanced treatment results for esophageal cancer. We evaluated the efficacy and the toxicity of a novel regimen of daily low-dose nedaplatin (cis-diammine-glycolatoplatinum) and continuous infusion of 5-fluorouracil (5-FU) with radiation in patients with esophageal squamous cell carcinoma.</p> <p>Methods</p> <p>Between January 2003 and June 2008, 33 patients with clinical stage I to IVB esophageal squamous cell carcinoma were enrolled. Nedaplatin (10 mg/body/day) was administered daily and 5-FU (500 mg/body/day) was administered continuously for 20 days. Fractionated radiotherapy for a total dose of 50.4-66 Gy was administered together with chemotherapy. Additional chemotherapy with nedaplatin and 5-FU was optionally performed for a maximum of 5 courses after chemoradiotherapy. The primary end-point of this study was to evaluate the tumor response, and the secondary end-points were to evaluate the toxicity and the overall survival.</p> <p>Results</p> <p>Twenty-two patients (72.7%) completed the regimen of chemoradiotherapy. Twenty patients (60.6%) achieved a complete response, 10 patients (30.3%) a partial response. One patient (3.0%) had a stable disease, and 2 (6.1%) a progressive disease. The overall response rate was 90.9% (95% confidence interval: 75.7%-98.1%). For grade 3-4 toxicity, leukopenia was observed in 75.8% of the cases, thrombocytopenia in 24.2%, anemia in 9.1%, and esophagitis in 36.4%, while late grade 3-4 cardiac toxicity occurred in 6.1%. Additional chemotherapy was performed for 26 patients (78.8%) and the median number of courses was 3 (range, 1-5). The 1-, 2- and 3-year survival rates were 83.9%, 76.0% and 58.8%, respectively. The 1- and 2-year survival rates were 94.7% and 88.4% in patients with T1-3 M0 disease, and 66.2% and 55.2% in patients with T4/M1 disease.</p> <p>Conclusion</p> <p>The treatment used in our study may yield a high complete response rate and better survival for each stage of esophageal squamous cell carcinoma.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00197444</p

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Development of a novel cytoplasmic hydroxyl radical-targeting antioxidant (TA293) that suppresses cellular senescence, inflammation, and apoptosis: DOI: 10.14800/ics.1539

Hydroxyl radicals (•OH) exhibit the strongest oxidation potential of any reactive oxygen species (ROS) and react non-specifically with cellular components, such as nucleic acids, lipids and proteins. While mitochondrial •OH incites oxidative damage resulting in mitochondrial dysfunction, the actions of cytoplasmic •OH remain unknown as no cytoplasmic •OH-specific scavenger has been identified to date. To solve this problem, we developed the cytoplasm- and mitochondrion-specific •OH-targeted scavengers TA293 and mitoTA293, respectively. As expected, TA293 and mitoTA293 scavenged •OH, but not O2– or H2O2. Notably, TA293 scavenged pyocyanin-induced cytoplasmic •OH, but not mitochondrial radicals induced by antimycin A. Conversely, mitoTA293 scavenged •OH only in the mitochondria in vivo and in vitro. Interestingly, we found that cytoplasmic •OH plays a central role in cytoplasm ROS-induced oxidative stress, which potentiates cellular senescence, inflammation, and apoptosis in the kidney and lung. Based on these findings, we believe that TA293 could be a novel tool to study the effects of •OH damage within the cytoplasm

Effects of Immediate and Delayed Cementations for CAD/CAM Resin Block after Alumina Air Abrasion on Adhesion to Newly Developed Resin Cement

The purpose of this study was to evaluate the effect of one week of Computer-aided design/Computer-aided manufacturing (CAD/CAM) crown storage on the μTBS between resin cement and CAD/CAM resin composite blocks. The micro-tensile bond strength (μTBS) test groups were divided into 4 conditions. There are two types of CAD/CAM resin composite blocks, namely A block and P block (KATANA Avencia Block and KATANA Avencia P Block, Kuraray Noritake Dental, Tokyo, Japan) and two types of resin cements. Additionally, there are two curing methods (light cure and chemical cure) prior to the μTBS test—Immediate: cementation was performed immediately; Delay: cementation was conducted after one week of storage in air under laboratory conditions. The effect of Immediate and Delayed cementations were evaluated by a μTBS test, surface roughness measurements, light intensity measurements, water sorption measurements and Scanning electron microscope/Energy dispersive X-ray spectrometry (SEM/EDS) analysis. From the results of the μTBS test, we found that Delayed cementation showed significantly lower bond strength than that of Immediate cementation for both resin cements and both curing methods using A block. There was no significant difference between the two types of resin cements or two curing methods. Furthermore, water sorption of A block was significantly higher than that of P block. Within the limitations of this study, alumina air abrasion of CAD/CAM resin composite restorations should be performed immediately before bonding at the chairside to minimize the effect of humidity on bonding