Redox control in the pathophysiology of influenza virus infection.

Triggered in response to external and internal ligands in cells and animals, redox homeostasis is transmitted via signal molecules involved in defense redox mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Cellular oxidation is not necessarily harmful per se, but its effects depend on the balance between the peroxidation and antioxidation cascades, which can vary according to the stimulus and serve to maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and redox control using IV infection as an example. We discuss the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS accumulation and the diversity of IV infection. We also summarize the potential anti-IV agents available currently that act by targeting redox biology/pathophysiology.

Photobiomodulation therapy inhibits oral submucous fibrosis in mice.

OBJECTIVES: Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder. However, the best therapeutic treatment for OSMF remains uncertain. Our previous study showed that photobiomodulation (PBM) therapy and forskolin could reduce arecoline-induced fibrosis reactions via the cAMP pathway. The present study aimed to establish an animal model of areca nut extract (ANE)-induced OSMF and to evaluate the therapeutic potential of PBM and forskolin for ANE-induced OSMF. SUBJECTS AND METHODS: The mice were divided into five groups. The buccal tissues were harvested for histomorphological analysis and immunoblotting. RESULTS: Our results showed that PBM significantly reduced the development of ANE-induced OSMF, quantified by changes in submucosal layer thickness and collagen deposition. Additionally, PBM could extensively reduce the protein expression of the fibrotic marker genes alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) in buccal submucous lesions. However, forskolin treatment significantly decreased the protein expression of fibrotic marker genes but slightly decreased the observed histomorphological changes. CONCLUSIONS: We established an ANE-induced OSMF mouse model, which also provided a model for the development of a therapeutic treatment for OSMF. The anti-fibrotic effects of PBM and forskolin may be useful for clinical interventions.

Influence of cavity depth and restoration of non-carious cervical root lesions on strain distribution from various loading sites.

BACKGROUND: We aimed to investigate the load-induced strain variation in teeth with unrestored and resin-based composite restored non-carious cervical lesions (NCCLs). METHODS: Twelve extracted premolars were provided for measuring buccal-side root NCCLs. Strain gauges were fixed at four measuring sites of each tooth, two at the buccal surface and two at the lingual surface. NCCLs were prepared with occlusal margins at the cemento-enamel junction. A static 9-kg load was applied at seven occlusal loading points: buccal cusp tip (BC), inner inclination of the BC, lingual cusp tip (LC), inner inclination of the LC, center of the mesial marginal ridge or distal marginal ridge, and center of the central groove. The strain was detected at each site in teeth with NCCL depths of 0 (control), 0.5, 1.0, and 1.5 mm. Each NCCL was restored using an adhesive composite resin, and the strains were re-measured. RESULTS: The strains at the NCCL occlusal and gingival margins decreased with increasing defect depths, and the effect was significant when the depth of the defect was 1.5 mm. Loading on the buccal and lingual cusps induced prominent strain variation. The strains at all depth distribution recovered to nearly intact conditions when the NCCLs were restored. CONCLUSIONS: NCCLs at 1.5 mm depth are detrimental, but they can be restored using resin composites. CLINICAL SIGNIFICANCE: The existence of NCCLs should not be ignored. The depth of the NCCL may affect the progression of the lesion. Resin composite restoration is an appropriate method for preventing persistent NCCL deterioration.

Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer.

The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016;34:2613-2624.

Correlation Between Blood Loss and Patient-Related Factors in the Bilateral Parasymphyseal Osteotomy.

The aim of this study was to determine the correlation between pre- and postsurgical loss of blood and blood components among patients undergoing treatment of facial deformities by bilateral parasymphyseal osteotomy (BPsO).The pre- and postoperative values of blood components were determined in 30 facial deformity patients who underwent orthognathic surgery by hypotensive anesthesia. Correlations among the blood loss, sex, age, operation time, and reduced values of blood components were assessed by a correlation matrix. The mean blood loss and operation time were 437.5 (± 52.5) mL and 355.8 (± 209.42) minutes, respectively. Two patients included in this study had required blood transfusion. The mean reduced red blood cell (× 10/µL), hemoglobin (g/dL), and hematocrit (%) were -1.02, -2.98, and -9.18, respectively. There was no significant correlation between blood loss and other related factors (eg, age, operation time, and reduced blood components). All patients, however, showed significantly lower values of blood components after surgery. In conclusion, no significant factor was associated with blood loss and reduced blood components among patients undergoing BPsO. Furthermore, hypotensive anesthesia is a well-accepted method to reduce blood loss during orthognathic surgery.

Analysis of maximum mouth opening and its related factors in 3- to 5-year-old Taiwanese children.

Maximum mouth opening (MMO) can reflect the function of the dentofacial musculature and joint system, and routine oral examinations should include its assessment. To diagnose abnormalities using MMO measurements, it is necessary to establish the normal range of MMO; however, few studies have investigated this subject in Taiwan. Therefore, the purposes of this study were to determine the normal MMO range in 3- to 5-year-old preschool children and to investigate the factors correlated with MMO. We examined the interincisal distance, defined as the distance between the edges of the upper and lower incisors, in 518 preschool children (age range 3-5 years; 271 boys and 247 girls) with a plastic sliding caliper. The MMO on both sides of the mouth and mouth width (MW) was measured 3 times. No differences in MMO were found between the genders. The interincisal distance was 37.47 (±4.11) mm for boys and 36.93 (±3.85) mm for girls, whereas the mean MMO was 37.21 (±3.99) mm. The MMO increased with the increasing age of the children, and the mean value of MMO in children aged 3, 4, and 5 was 35.31 (±4.03), 36.61 (±3.79), and 38.31 (±3.88) mm, respectively. Furthermore, MMO was found to correlate with weight and MW. MMO increased by 0.19 mm per increased weight and 0.37 mm per increased MW. The mean value of MMO in 3- to 5-year-old preschool children was 37.21 (±3.99) mm. MMO in 3- to 5-year-old preschool children increased with age and was correlated with weight and MW.

Expression of a splice variant of CYP26B1 in betel quid-related oral cancer.

Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.

Long-term sequential receptor activator of NF-κB ligand (RANKL) and osteoprotegrin (OPG) expression in lipopolysaccharide-induced rat periapical lesions.

BACKGROUND: Long-term sequential expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegrin (OPG) in lipopolysaccharide (LPS)-induced rat periapical lesions has not been studied. MATERIALS: Seventy-two 4-week-old Wistar rats were divided into eight experimental groups and one control group (eight animals in each). METHODS: Lipopolysaccharide-induced periapical lesions were produced in rats by occlusal exposure of the pulp of their lower first molars in all experimental groups but not the control group. The extent of periapical destruction was measured by radiographic imaging. RANKL and OPG mRNA were measured in all tissue sections containing the periapical lesions as well as the control group every week from week 1 to week 8 by real-time quantitative reverse transcription polymerase chain reaction. RANKL and OPG protein were determined by immunohistochemistry. Osteoclasts were identified by enzyme histochemistry. RESULTS: The sequential changes in the mRNA and protein expression of RANKL and OPG were largely compatible with the occurrence of osteoclasts histologically and enzymes histochemically, as well as the mean areas of the periapical lesions radiographically during long-term observation of the LPS-induced rat periapical lesions. CONCLUSION: This study may be the first to demonstrate the long-term RANKL and OPG expression every week from week 1 to week 8 using LPS to produce periapical infection in a Wistar rat model. The long-term findings of high expressions of RANKL and OPG further extend the potential application of the Wistar rat model for future experimental trials using RANKL inhibitor to evaluate the treatment outcome for LPS-induced rat periapical lesions.

Detrimental effects of maternal lead exposure during pregnancy and lactation on molar development in the young rat.

The purpose of this animal study was to investigate the influence of maternal lead exposure during pregnancy and lactation on molar development in the offspring. Scanning electron microscopy revealed no significant differences in the molar morphology among the groups. However, in all the experimental groups, deep, wide cracks were found in the occlusal enamel. Further, the experimental groups had smaller molar diameters than the control group, lead exposure during lactation had a greater influence on the molar size in the offspring, and the groups with the higher dose of lead exposure during pregnancy and lactation had significantly smaller molar sizes than the groups that received the lower dose. The mesiodistal and buccolingual diameters of molars were measured as 3.10 ± 0.07 and 1.95 ± 0.04 mm for control group, 2.97 ± 0.08 and 1.94 ± 0.01 mm for lactation group of low dose, 2.96 ± 0.05 and 1.84 ± 0.02 mm for lactation group of high dose, 3.09 ± 0.06 and 1.94 ± 0.04 mm for pregnancy group of low dose, and 3.02 ± 0.06 and 1.85 ± 0.06 mm for pregnancy group of high dose, respectively.

Influence of commercial adhesive with/without silane on the bond strength of resin-based composite repaired within twenty-four hours.

BACKGROUND/PURPOSE: It is not clear whether the ground surface of resin-based composite (RBC) polymerized requires the application of an adhesive with/without a silane to improve bond strength. This study investigated the bond strength of RBC repaired within 24 h via the application of adhesive with/without a silane. MATERIALS AND METHODS: Seventy RBC blocks were prepared and assigned to either 0 or 24 h repair stage. Each stage was divided into seven groups: a control group with no surface roughening or applied adhesive, a surface-roughened group with no applied adhesive, two surface-roughened groups treated with a G-aenial Bond adhesive and a BeautiBond Multi adhesive, two surface-roughened groups treated with the previously-mentioned adhesives as well as silane coupling agents, and one group treated with a Single Bond Universal silane-containing adhesive. Microtensile bond strength (µTBS) measurements were performed after the repaired RBC blocks of each group (n = 5) had been immersed in a 37 °C water bath for 24 h. The failure mode of each sample was determined, and the data were analyzed via one-way analysis of variance and Dunnett's test (p = 0.05). RESULTS: Regardless of the repair stage, the µTBS values of the adhesive-only and silane-adhesive groups did not differ significantly from those of the control group (p > 0.05). Only the no-adhesive groups exhibited a significantly time-dependent increase in adhesive failure rate. CONCLUSION: Our results suggest that the application of adhesives either with or without silane can significantly increase the bond strength of repairs to RBCs polymerized within 24 h.

Effect of toothbrush/dentifrice abrasion on weight variation, surface roughness, surface morphology and hardness of conventional and CAD/CAM denture base materials.

We evaluated the effect of toothbrush/dentifrice brushing on the weight variation and surface properties of different denture bases. Four denture base materials (conventional heat cure, high impact, CAD/CAM, and polyamide resins) were subjected to toothbrushing abrasion (50,000 strokes). The weight value, surface roughness, and topography of each group were determined before and after toothbrushing. The hardness was measured by the Vickers hardness test. Data were analyzed using ANOVA and Bonferroni tests. After toothbrushing, the weight of the polyamide resin had significantly increased; significant weight losses were observed for conventional heat cure and high impact resins, but none for the CAD/CAM resin. The surface roughness of each group increased significantly owing to the wear caused by toothbrushing. The weight variation and surface roughness were not affected by the hardness. Our results suggested that denture base materials deteriorate after brushing with toothpaste, in which the polyamide resin exhibited lower levels of abrasion.

The impact of the COVID-19 epidemic on the utilization of dental services and attitudes of dental residents at the emergency department of a medical center in Taiwan.

BACKGROUND/PURPOSE: Dental visits are a high risk activity during the COVID-19 pandemic. This study investigated the utilization of emergency dental services and clinical practical attitudes of dental residents in this period. MATERIALS AND METHODS: Retrospective chart data from 13th November 2019 to 31st March 2020 in Kaohsiung Medical University Hospital, Taiwan were used. We obtained electronic medical records to review data from 515 patients who visited the emergency department with dental complaints and we contacted the 26 residents assigned to act as primary care providers to participate in this study. RESULTS: After the COVID-19 outbreak, 17% fewer patients had dental emergency utilization at a hospital emergency center relative to the previous period. A survey of residents also showed a decline in the number of patients. There were no significant differences of patients' problems and diagnoses between the two periods. After the COVID-19 outbreak, 61.5% of the residents were afraid of being infected by a patient's disease and the proportions of dentists wearing waterproof gowns, face shields, and surgical hair caps were 76.9%, 88.5%, and 76.3%, respectively. These variables increased significantly after the outbreak of COVID-19. CONCLUSION: Despite the trend of a decreased number of patients, their utilization of dental emergency services seems to be similar before and after the COVID-19 outbreak, possibly related to strict hospital infection control policies and the relatively low number of COVID-19 confirmed patients internationally at that time.

A Study of Low Young's Modulus Ti-15Ta-15Nb Alloy Using TEM Analysis.

The microstructural characteristics and Young's modulus of the as-cast Ti-15Ta-15Nb alloy are reported in this study. On the basis of the examined XRD and TEM results, the microstructure of the current alloy is essentially a mixture (α + ß+ α' + α″ + ω + H) phase. The new H phase has not previously been identified as a known phase in the Ti-Ta-Nb alloy system. On the basis of examination of the Kikuchi maps, the new H phase belongs to a tetragonal structural class with lattice parameters of a = b = 0.328 nm and c = 0.343 nm, denoting an optimal presentation of the atomic arrangement. The relationships of orientation between these phases would be {0001}α//{110}ß//{1¯21¯0}ω//{101¯}H and (011¯0)α//(11¯2)ß//(1¯010)ω//(121)H. Moreover, the Young's modulus of the as-cast Ti-15Ta-15Nb alloy is approximately E = 80.2 ± 10.66 GPa. It is implied that the Young's modulus can be decreased by the mixing of phases, especially with the presence of the H phase.

Effect of Ti2Cu precipitation on antibacterial property of Ti-5Cu alloy.

To instill pure Ti with an antibacterial effect, Cu was added by metallurgical alloying to produce Ti-5 wt% Cu alloy (Ti-5Cu alloy). The precipitation of the likes of Ti2Cu in a Ti-Cu alloy is one of the factors that influences its antibacterial property. However, in the present study, Ti-5Cu alloy precipitates with different microstructures were obtained by applying heat treatment at different temperatures and for different durations. After the heat treatment, metallographic, microstructure, and element analyses were performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) combined with energy dispersive X-ray spectroscopy (EDS). The antibacterial property of the Ti-5Cu alloy was assessed by the plated-count method using Escherichia coli (E. coli). The microstructure analysis revealed that the solution-treated alloy had no precipitation, while the aged alloy contained precipitations of intermetallic Ti2Cu compound. The aged alloy exhibited better antibacterial performance as the duration of the aging treatment increased. The optimal heat treatment for Ti-5Cu was found to be aging at 700 °C for 4 h, at which point the nucleation formation of the Ti2Cu particles would assume an acicular morphology. These acicular precipitates exhibit a high Cu content which, in turn, influences the antibacterial performance.

Three-dimensional finite element modeling from CT images of tooth and its validation.

The aim of this study was to develop a three-dimensional (3D) finite element (FE) model of a sound extracted human second premolar from micro-CT data using commercially available software tools. A detailed 3D FE model of the tooth could be constructed and was experimentally validated by comparing strains calculated in the FE model with strain gauge measurement of the tooth under loading. The regression coefficient and its standard error in the regression analysis between strains calculated by the FE model and measured with strain gauge measurement were 0.82 and 0.06, respectively, and the correlation coefficient was found to be highly significant. These results suggested that an FE model reconstructed from micro-CT data could be used as a valid model to estimate the actual strains with acceptable accuracy.

Influence of the acidity of electrolyzed water on the microhardness of inner layer dentin.

BACKGROUND/PURPOSE: Electrolyzed water has been identified as an effective disinfectant that could represent as an alternative to sodium hypochlorite. Unfortunately, it remains unclear whether the texture or physical properties of dentin are affected by the application of electrolyzed water of different acidities. This study was aimed to assess the influence of electrolyzed waters with differing pHs on the demineralizing of inner dentin. MATERIALS AND METHODS: The coronal superficial dentin of 20 human molars was exposed and further bisected into two pieces perpendicular to the dentin surface. The samples were immersed in strongly acidic electrolyzed water (AW group), neutral electrolyzed water (NW group), 5% sodium hypochlorite (positive control, NL group), or deionized water (negative control, DW group). Microhardness of the inner layer dentin was measured at a depth of 25 and 50 µm beneath the superficial surface layer every 5 up to 60 min. RESULTS: At a depth of 25 µm, microhardness decreased with increasing immersion time in all but the DW group. The AW group exhibited a decreasing trend from the first 5 min that became significant after 35 min of immersion and was the most rapid decrease in the four groups. The rate of decline in the NW group was low and similar to that of the NL group. Both NW and NL groups exhibited significantly less demineralization than the AW group after 15 min of immersion. No significant microhardness change was found at a depth of 50 µm in any of the samples. CONCLUSION: AW produces a more pronounced softening of dentin than NW at a depth of 25 µm.

Electropolishing of CP titanium and its alloys in an alcoholic solution-based electrolyte.

A newly developed electropolishing system, equipped with an original agitation function for an electrolyte and using a safe electrolyte composed of an alcoholic solution, was applied for wrought and cast CP titanium and its alloys. Surface roughness and morphology of the polished surfaces were then examined. Under an electrolytic condition of 70-75 V, 2.0 kA/m2, and 30 degrees C, wrought CP Ti and Ti-6Al-4V alloy achieved an apparent mirror-like finishing with an average surface roughness (Ra) of 0.03 and 0.12 microm respectively. Under the same condition, on the other hand, cast CP Ti and Ti-6Al-7Nb alloy produced rougher polished surfaces with average Ra values of 0.67-0.80 microm, and the finishing was apparently shiny, but not mirror-like. SEM observation of the polished surfaces showed that wrought CP Ti was even and completely featureless, while wrought Ti-6Al-4V alloy was pitted. For cast CP Ti, a needle-like phase containing traces of iron was observed on the polished surface.

Intensity of singular stress fields of wedge-shaped defect in human tooth due to occlusal force before and after restoration with composite resins.

Wedge-shaped defects are frequently observed on the cervical region of the human tooth. Previously, most studies explained that improper tooth-brushing causes such defects. However, recent clinical observation suggested that the repeated stress due to occlusal force may induce the formation of these wedge-shaped defects. In this study, therefore, two-dimensional human tooth models are considered with and without a wedge-shaped defect by applying the finite element method. To evaluate large stress concentrations accurately, a method of analysis is discussed in terms of the intensity of singular stress fields appearing at the tip of the sharp wedge-shaped defect. The effects of the position and direction of occlusion on the intensity of singular stress fields are discussed before and after restoration with composite resins.

Milling properties of low temperature sintered zirconia blocks for dental use.

To investigate the milling properties of different yttria-tetragonal zirconia polycrystalline (Y-TZP) block materials by applying a dental computer numerical control (CNC) milling center. Low temperature sintering zirconia block denoted by KMUZ (experimental) with two commercial zirconia blocks for T block made in Taiwan and a G block made in Germany were compared for the milling properties. Seventy-two specimens were milled using the same CNC milling center, and properties were evaluated by measuring the weight loss (g), milling time (s), margin integrity (%) and broken diameter (µm). The crystalline phases contents were identified by X-ray diffraction and the microstructures of the sintering specimens were observed by scanning electron microscopy and transmission electron microscopy. The mean milling time of G and KMUZ were significantly shorter than T (P<0.05). The KMUZ samples exhibited the least weight loss among the three kinds of blocks (P<0.05). The percentages of marginal integrity after milling were high in G and KMUZ but low in T (P<0.05). The mean broken diameters were from 90µm to 120µm. The phase transformation of t-ZrO2 (KMUZ: 7.4%, G: 5.9%, T: 3.2%) to m-ZrO2 when facing the milling pressure in ZrO2 blocks was observed by XRD. The result of TEM microstructure of KMUZ revealed that Y and Si were soluble in grain boundaries. The results show that the milling properties of KMUZ were better than one commercial T and near the G. The hindered grain growth, as a result of the Y3+ content in the grain boundaries, also plays a role in promoting the abnormal grain growth of 3Y-TZP.

Low-power laser irradiation inhibits arecoline-induced fibrosis: an in vitro study.

Oral submucous fibrosis (OSF) is a potentially malignant disorder that is characterized by a progressive fibrosis in the oral submucosa. Arecoline, an alkaloid compound of the areca nut, is reported to be a major aetiological factor in the development of OSF. Low-power laser irradiation (LPLI) has been reported to be beneficial in fibrosis prevention in different damaged organs. The aim of this study was to investigate the potential therapeutic effects of LPLI on arecoline-induced fibrosis. Arecoline-stimulated human gingival fibroblasts (HGFs) were treated with or without LPLI. The expression levels of the fibrotic marker genes alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF/CCN2) were analysed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) and western blots. In addition, the transcriptional activity of CCN2 was further determined by a reporter assay. The results indicated that arecoline increased the messenger RNA and protein expression of CCN2 and α-SMA in HGF. Interestingly, both LPLI and forskolin, an adenylyl cyclase activator, reduced the expression of arecoline-mediated fibrotic marker genes and inhibited the transcriptional activity of CCN2. Moreover, pretreatment with SQ22536, an adenylyl cyclase inhibitor, blocked LPLI's inhibition of the expression of arecoline-mediated fibrotic marker genes. Our data suggest that LPLI may inhibit the expression of arecoline-mediated fibrotic marker genes via the cAMP signalling pathway.