Anti-glioblastoma effects of nanomicelle-curcumin plus erlotinib.

Glioblastoma (GBM), one of the most significant brain neoplasms, is characterized by high metastasis and recurrence. Crossing the blood-brain barrier is one of the main therapeutic obstacles, seriously hampering therapeutic agents entering the brain. This research investigated the co-delivery of erlotinib and curcumin via nanomicelles for enhancing anti-GBM treatment in vitro. For this purpose, curcumin and nanomicelle-curcumin (50 µM) were investigated alone and also with erlotinib (50 µM) in U87 glioblastoma cells. The cell viability of U87 cells after exposure to curcumin/nanomicelle curcumin/erlotinib and their combinations was measured by CCK-8 assay. The expression of the Wnt signaling-related genes was measured by qRT-PCR assay. The altered expression of NF-kB and proteins associated with angiogenesis, apoptosis, and autophagy were investigated by western blot assay. Compared with the control, all treatments reduced the viability of U87 glioblastoma cells. Furthermore, the level of proteins related to angiogenesis and Wnt pathway-associated genes in the nanomicelle-curcumin + erlotinib group were significantly decreased compared to the curcumin, erlotinib, and control groups. Each treatment regulated autophagy and apoptosis-associated proteins. Total phospho-NF-κB (p65) and total NF-κB (p65) declined in each treatment at the protein levels. Overall, nanomicelle-curcumin alone or combined with erlotinib showed anti-GBM activity in the U87 cell line by regulating the signaling pathways in GBM pathogenesis and thus may be a promising nanodrug candidate for application in the field of GBM therapy.

Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways.

Glioblastoma (GBM) is the most serious brain tumor and shows a high rate of drug resistance. Wnt signaling is a very important pathway in GBM that can activate/inhibit other pathways, such as apoptosis and autophagy. In this study, we evaluated the efficacy of a combination of temozolomide (TMZ) plus curcumin or nanomicellar-curcumin on the inhibition of GBM growth in vitro, via effects on autophagy, apoptosis, and the Wnt signaling pathway. Two concentrations of curcumin and nanomicellar-curcumin (i.e., 20 µM and 50 µM) alone, and in combination with TMZ (50 µM) were used to induce cytotoxicity in the U87 GBM cell line. Wnt signaling-, autophagy-, and apoptosis-related genes were assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blots. All treatments (except 20 µM curcumin alone) significantly decreased the viability of U87 cells compared to controls. Curcumin (50 µM), nanomicellar-curcumin alone and in combination with TMZ significantly decreased the invasion and migration of U87 cells. Autophagy-related proteins (Beclin 1, LC3-I, LC3-II) were significantly increased. Apoptosis-related proteins (Bcl-2 and caspase 8) were also significantly increased, while Bax protein was significantly decreased. The expression levels of Wnt pathway-associated genes (ß-catenin, cyclin D1, Twist, and ZEB1) were significantly reduced.

Glass ionomer cements as fissure sealing materials: yes or no?: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate the ability of glass ionomer cements (GICs) and resin-based sealants (RBSs) to prevent the occurrence of caries and their retention in standards-based clinical studies. TYPES OF STUDIES REVIEWED: The authors conducted a literature search (from database inception through September 20, 2017) to identify studies for inclusion in this systematic review. The authors assessed the quality of the evidence with the modified Jadad scale and performed the meta-analysis by using a random-effects model. RESULTS: The authors considered 20 studies on caries prevention and 28 studies on retention that met the inclusion criteria for the meta-analysis. The results of the meta-analysis for caries development showed no significant difference (odds ratio, 0.938; 95% confidence interval, 0.647 to 1.359; P = .734). However, the result for the retention rate showed the advantage of RBSs (odds ratio, 6.006; 95% confidence interval, 3.226 to 11.183; P = .000). CONCLUSIONS AND PRACTICAL IMPLICATIONS: There was no difference between the percentage of caries development with use of GICs as fissure sealing material compared with that for the conventional RBSs, but the retention rate of conventional RBSs was much higher than that of the GICs.

Mineral Trioxide Aggregate Partial Pulpotomy Versus Formocresol Pulpotomy: A Randomized, Split-Mouth, Controlled Clinical Trial with 24 Months Follow-Up.

PURPOSE: The purpose of this study was to evaluate the clinical and radiographic success rates of mineral trioxide aggregate partial pulpotomy (PP) compared to formocresol pulpotomy (FP) in human primary molars. METHODS: In this randomized, controlled, split-mouth, clinical trial, 25 healthy five- to eight-year-olds, with 50 carious primary mandibular second molars lacking clinical and radiographic evidence of pulp pathology, were selected. The selected teeth were randomly assigned into two groups, PP and FP, for vital pulp therapy. Stainless steel crowns were placed as final restorations for both groups. Clinical and radiographic evaluation at six, 12, and 24 months used the following criteria for failure: pain; swelling; sinus tract; mobility; internal or external root resorption; furcation or periapical radiolucency; and widening of periodontal ligament space. The data were analyzed using a binary logistic generalized estimating equation model. RESULTS: At the 12-month and 24-month follow-ups, one child and three children, respectively, were lost to follow-up. At the 24-month follow-up, the clinical, radiographic, and overall success rates of PP were 90.9 percent, 90.5 percent, and 81.8 percent versus FP success of 100 percent, 95.2 percent, and 95.2 percent, respectively. CONCLUSION: There were no significant differences between clinical, radiographic, and overall success rate of mineral trioxide aggregate partial pulpotomy and formocresol pulpotomy overall 24 months.

Microbial microleakage assessment of class V cavities restored with different materials and techniques: A laboratory study.

BACKGROUND: The aim of this study was to compare microbial microleakage of class V cavities restored with different materials and techniques using a microbial leakage assessment method. MATERIALS AND METHODS: One hundred extracted, caries-free, human maxillary premolars were randomly divided into five groups. Group 1: Resin-modified glass ionomer (RMGI), Group 2: Closed sandwich with flowable composite + nanohybrid composite, Group 3: Nanohybrid composite, Group 4: Closed sandwich with RMGI + nanohybrid composite, and Group 5: Flowable composite + nanohybrid composite that were co-cured together ("snow-plow" technique). A microbial penetration method utilizing Streptococcus mutans as an indicator was tested for leakage assessment. Data were analyzed and the significance level was α =0.05. RESULTS: The log-rank test indicated a statistically significant difference in leakage rates among the five groups (P = 0.008). Mantel-Cox log-rank test indicated statistically significant differences in microleakage rates between Groups 1 and 3 (P = 0.029), between Groups 2 and 5 (P = 0.005), and between Groups 3 and 5 (P = 0.002). CONCLUSION: With respect to the limitations of an in vitro study, our findings suggest that adding a thin layer of flowable composite or RMGI under nanohybrid composite in class V cavities did not decrease the bacterial leakage rate, whereas use of the "snow-plow" technique caused an increase in the microleakage rate.

Can tert-butylhydroquinone improve the healing of extracted tooth socket in rats?

BACKGROUND: Tooth extraction causes an open wound in the soft and hard tissues. During the inflammatory phase of the healing process, a large amount of free radicals are produced and cause oxidative stress, which leads to tissue damage and delayed wound healing. Thus, in this study, we evaluated the effect of tert-butylhydroquinone (TBHQ), as an antioxidant, on the healing process of tooth sockets in rats. MATERIALS AND METHODS: To conduct this experimental study, male Wistar rats (n = 42) were divided into two groups. In each case, one upper second molar was extracted under general anesthesia. After the extraction, the tooth sockets of the experimental group were treated with a 0.02% TBHQ solution (0.1 ml) while the same volume of distilled water placed in the sockets of the control group. On days 3, 7, and 21 postoperatively, 7 rats from each group were euthanized, and histological slides were prepared from their tooth sockets. The prepared slides were examined histopathologically using a light microscope and compared using an independent two-sample t-test. The significance level was set at 0.05. RESULTS: In the experimental group, a statistically significant (P = 0.003) increase in granulation tissue was observed on day 3, in comparison to the control group. The extent of bony trabeculation was also significantly higher in the TBHQ-treated group than in the control group on day 21 (P < 0.001). CONCLUSION: Considering the limitations of an experimental study, it can be concluded that TBHQ may enhance the healing of the hard tissue in the tooth sockets.

Preparation before acid etching in fissure sealant therapy: yes or no?: A systematic review and meta-analysis.

BACKGROUND: The authors of this systematic review and meta-analysis had 2 aims: to evaluate fissure sealant retention with and without the use of a preparation method and to compare fissure sealant retention using the preparation-only method before sealant placement with the conventional acid-etching procedure. TYPES OF STUDIES REVIEWED: The authors conducted a literature search (from database inception through June 2, 2016) to identify studies for inclusion in this systematic review. The authors assessed the quality of the evidence with the modified Jadad scale and performed the meta-analysis by using a random-effects model. RESULTS: The authors considered 12 studies (8 for the first part and 4 for the second part) that met the inclusion criteria for the systematic review and meta-analysis. In the analysis of the first part of the systematic review, the authors found that the preparation method before acid etching had a significant positive effect on fissure sealant retention (odds ratio, 3.262; 95% confidence interval, 1.782-5.971; P = .001). In the analysis of the second part of the systematic review, the authors found that there were no significant differences between the preparation-only method and the conventional acid-etching method in terms of fissure sealant retention (odds ratio, 1.241; 95% confidence interval, 0.534-2.888; P = .616). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The use of a preparation method before fissure sealant application can increase sealant retention. However, preparation alone cannot substitute the conventional acid-etching method before sealant placement.

Children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia: A randomized controlled trial.

BACKGROUND: Topical anesthesia has been widely advocated as an important component of atraumatic administration of intraoral local anesthesia. The aim of this study was to use direct observation of children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia. MATERIALS AND METHODS: Forty-eight children participated in this randomized controlled clinical trial. They received two separate inferior alveolar nerve block or primary maxillary molar infiltration injections on contralateral sides of the jaws by both cotton-roll vibration (a combination of topical anesthesia gel, cotton roll, and vibration for physical distraction) and control (routine topical anesthesia) methods. Behavioral pain reactions of children were measured according to the author-developed face, head, foot, hand, trunk, and cry (FHFHTC) scale, resulting in total scores between 0 and 18. RESULTS: The total scores on the FHFHTC scale ranged between 0-5 and 0-10 in the cotton-roll vibration and control methods, respectively. The mean ± standard deviation values of total scores on FHFHTC scale were lower in the cotton-roll vibration method (1.21 ± 1.38) than in control method (2.44 ± 2.18), and this was statistically significant (P < 0.001). CONCLUSION: It may be concluded that the cotton-roll vibration method can be more helpful than the routine topical anesthesia in reducing behavioral pain reactions in children during local anesthesia administration.

Adhesive systems under fissure sealants: yes or no?: A systematic review and meta-analysis.

BACKGROUND: The authors of this systematic review and meta-analysis had 2 aims: to evaluate fissure sealant retention with and without the use of an adhesive system and to compare fissure sealant retention using etch-and-rinse adhesive systems versus self-etching adhesive systems. TYPES OF STUDIES REVIEWED: The authors conducted a literature search (all articles published through November 1, 2015) to identify studies for inclusion in this systematic review. They assessed the quality of the evidence provided using the modified Jadad scale and performed meta-analyses using a random-effects model. RESULTS: The authors considered 12 studies that met the inclusion criteria for the systematic review. In addition, they used 5 of 9 studies related to the first part of the study and 3 of 4 studies related to the second part of the study that met the inclusion criteria for meta-analysis. In the analysis of the first part of the systematic review, the authors found that adhesive systems had a significant positive effect on fissure sealant (odds ratio, 3.294; 95% confidence interval, 1.292-8.401; P = .013). In the analysis of the second part of the systematic review, the authors found that etch-and-rinse adhesives were superior to self-etching adhesives in the fissure sealant procedure (odds ratio, 14.569; 95% confidence interval, 2.616-81.131; P = .002). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The use of adhesive systems beneath fissure sealants can increase the retention of fissure sealants. Also, when adhesive systems are used with fissure sealants, etch-and-rinse systems are preferable.

Phylogenetic Analysis of Selected Menthol-Producing Species Belonging to the Lamiaceae Family.

Menthol is an organic compound with diverse medicinal and commercial applications, and is made either synthetically or through extraction from mint oils. The aim of the present study was to investigate menthol levels in selected menthol-producing species belonging to the Lamiaceae family, and to determine phylogenetic relationships of menthol dehydrogenase gene sequence among these species. Three genus of Lamiaceae, namely Mentha, Salvia, and Micromeria, were selected for phytochemical and phylogenetic analyses. After identification of each species based on menthol dehydrogenase gene in NCBI, BLAST software was used for the sequence alignment. MEGA4 software was used to draw phylogenetic tree for various species. Phytochemical analysis revealed that the highest and lowest amounts of both essential oil and menthol belonged to Mentha spicata and Micromeria hyssopifolia, respectively. The species Mentha spicata and Mentha piperita, which were assigned to one cluster in the dendrogram, contained the highest amounts of essential oil and menthol while Micromeria species, which was in the distinct cluster and placed in the farther evolutionary distance, contained the lowest amount of essential oil and menthol. Phylogenetic and phytochemistry analyses showed that essential oil and menthol contents of menthol-producing species are associated with menthol dehydrogenase gene sequence.

Microleakage assessment of fissure sealant following fissurotomy bur or pumice prophylaxis use before etching.

BACKGROUND: A prolonged life of fissure sealant has always been the target for preventing caries in vulnerable newly erupted teeth. The use of preparatory techniques including bur introduction to the fissures is considered among such improving steps. MATERIALS AND METHODS: Ninety freshly extracted healthy maxillary premolar teeth were randomly selected for this investigation. Teeth were then divided into three fissure sealant preparatory groups of A: Fissurotomy bur + acid etch; B: Pumice prophylaxis + acid etch and C: Acid etch alone. Sealant was applied to the occlusal fissures of all specimens using a plastic instrument. This was to avoid any air trap under the sealant. Sample teeth were first thermocycled (1000 cycles, 20 s dwell time) and then coated with two layers of nail varnish leaving 2 mm around the sealant. This was then followed by immersion in basic fuchsin 3%. Processed teeth were sectioned longitudinally and examined under a stereomicroscope for microleakage assessment using a score of 0-3. Collected data was then subjected to Kruskall-Wallis Analysis of Variance and Mann-Whitney U-test. P > 0.05 was considered as significant. RESULTS: Teeth in fissurotomy bur and pumice prophylaxis groups had significantly reduced level of microleakage than those in acid etch alone (P = 0.005 and P = 0.003, respectively). CONCLUSION: Use of fissurotomy bur and pumice prophylaxis accompanied with acid etching appears to have a more successful reduction of microleakage than acid etch alone.

Association between dental caries and age-specific body mass index in preschool children of an Iranian population.

BACKGROUND: The aim of this study was to determine the association of dental caries and BMI-for-age in preschool children and whether BMI-for-age is similar or different between Severe Early Childhood Caries (S-ECC) and caries free children. MATERIALS AND METHODS: Four hundred preschool children aged 30-70 months were entered into this study. The parameters examined in this study were weight, height, BMI-for-age and number of decayed, extracted and filled surfaces of deciduous teeth (defs). Based on dental caries, the subjects were also divided into S-ECC and caries-free groups. Then data was analyzed by t-test, one-way ANOVA, multiple regression and logistic regression tests. RESULTS: The mean and SD of defs index was 8.37 ± 11.2. In the underweight, normal-weight, at risk of overweight and overweight groups, these values were 4.89 ± 10.8, 8.84 ± 11.8, 8.68 ± 10.6, and 10.39 ± 10.2, respectively. Multiple regression analysis revealed a statistically a significant direct association between BMI-for-age and defs index (P = 0.001) after adjusting for gender and age. The percentage of subjects who were caries free and S-ECC was 44.8% and 51.2%, respectively. Logistic regression analysis showed that there was statistically a significant inverse association between BMI-for-age scores and the frequency of caries-free (P = 0.001) and a significant direct association with S-ECC children (P = 0.001). CONCLUSIONS: The findings of this study demonstrated that there was an association between higher defs scores and severe early childhood caries with overweightness.

Microbial microleakage assessment of a new hydrophilic fissure sealant: a laboratory study.

PURPOSE: The purpose of this study was to compare microbial leakage of a new hydrophilic sealant with that of a conventional hydrophobic resin-based sealant. METHODS: One hundred extracted, caries-free, human maxillary premolars were randomly divided into five groups. Those in Groups 1, 2, and 3 had dry, wet, and artificial saliva-contaminated occlusal surfaces, respectively, and were sealed with a hydrophilic sealant, while those in Groups 4 and 5 had dry and wet occlusal surfaces, respectively, and were sealed with a hydrophobic sealant. A newly designed microbial penetration method utilizing Streptococcus mutans as an indicator was tested for leakage assessment. Data were analyzed using SPSS 15.0 software, and the significance level was set at α=0.05. RESULTS: The log rank test indicated a statistically significant difference in leakage rates among the five groups. Mantel-Cox log-rank test findings showed that Group 3 had the highest leakage rate, with Groups 2 and 4 having the lowest. There was no statistically significant difference in leakage rate between Groups 2 and 4. CONCLUSIONS: With respect to the limitations of an in vitro study, our findings suggest that hydrophilic sealants are an acceptable alternative to hydrophobic sealants.

Is there an association between early childhood caries and serum iron and serum ferritin levels?

BACKGROUND: Early childhood caries (ECC) is a virulent form of dental caries that can destroy the primary dentition of preschool children. The purpose of this study was to investigate a possible association between ECC with serum iron and serum ferritin levels. MATERIALS AND METHODS: Following the ethical approval, 204 children aged 24-71 months were recruited for a double-blind, randomized cross-sectional study. Each child was examined clinically for dental caries using the World Health Organization criteria in Rafsanjan, Iran. Decayed, extracted, and filled primary teeth (deft) index was used to measure the dental caries. To determine serum iron and serum ferritin levels 2 mL blood was collected from each child. Data were then analyzed by Pearson's correlation coefficient and t-test using SPSS-16.0 software. RESULTS: The mean values and their standard deviations of the deft index and levels of serum iron and ferritin were 2.4(± 3.3), 93.8(± 29.0) µg/dL and 63.1(± 32.2) ng/mL, respectively, with the two latter within. There was no significant difference between genders. Pearson's correlation coefficient showed that there was a statistically significant inverse association between ECC and serum iron level (P<0.05); but no association was found with the serum ferritin level. CONCLUSION: The deft index decreased significantly with increasing serum iron levels, but there was no association between ECC experience and serum ferritin levels.

Comparison of some salivary characteristics between children with and without early childhood caries.

BACKGROUND AND AIM: Early childhood caries (ECC) is one of the most common chronic childhood diseases. Saliva as a host factor plays an essential role in maintaining the integrity of oral structures. The aim of the present study was to compare resting salivary pH, buffering capacity, and secretory immunoglobulin A (sIgA), calcium, and phosphate concentrations between children with and without ECC. MATERIALS AND METHODS: In this cross-sectional study, samples of unstimulated saliva of 90 children (45 in ECC group and 45 in caries-free group) were taken with Scully method. The pH and buffering capacity were determined by pH meter. sIgA, calcium, and phosphate concentrations were quantitated with ELISA, CPC photometric, and phosphomolybdate/UV methods. RESULTS: The mean resting salivary pH was significantly higher among children without ECC and the buffering capacity was significantly better among this group (P = 0.002). The mean sIgA concentration was significantly higher among the ECC group (P = 0.015). There were no statistically significant differences between calcium and phosphate concentrations between the two groups. CONCLUSION: The higher mean resting salivary pH and better buffering capacity found in children without ECC are probably the contributing factors that protect against caries development; but further studies are needed to understand the effects of saliva and its characteristics and components on ECC.

Assessment of dental maturity of children aged 3.5 to 13.5 years using the Demirjian method in an Iranian population.

Radiographs of developing teeth are commonly used to assess dental maturity. The method for assessment of dental maturity first described by Demirjian is widely used and accepted. The aim of this study was to assess the accuracy of the Demirjian method in an Iranian population in order to compare the difference in dental maturity between these children with the data obtained in Canadian children and to determine whether there is a correlation between dental maturity and BMI-for-age. In this study, the orthopantomographs of 519 healthy children (264 boys and 255 girls) aged 3.5-13.5 years were reviewed and the dental age was determined by the Demirjian method. The chronological ages of the children were obtained by subtracting their birthdates from the date of taking the radiograph. Height and weight measurements were also recorded and the data were analyzed using SPSS-16 software. The Demirjian method overestimated the age by 0.15 and 0.21 years in boys and girls, respectively. Paired t-test analysis showed that these differences were statistically significant (P = 0.001). The increase in mean age difference initiated from the underweight group towards the overweight group, but this correlation was not statistically significant (P = 0.094). Based on the amount of differences between estimated dental age and chronological age in this investigation, the Demirjian method seems to be clinically applicable in the Iranian population.

An in vitro study of root and canal morphology of human deciduous molars in an Iranian population.

Dental caries is the most common chronic childhood disease. Deep caries and dental trauma are the two main etiologic factors responsible for pulp involvement. Better knowledge of the morphology of the root canals of deciduous teeth can improve the outcome of pulp treatment. In this study, 90 deciduous molar teeth (27 first mandibular molars, 27 first maxillary molars, 22 second mandibular molars and 14 second maxillary molars) were prepared using the clearing technique, and then dye was injected into the pulp cavity of each tooth. The roots of the teeth were examined under a stereomicroscope at × 10 magnification from different aspects. Measurements of root length and angulation were also recorded, and the data were analyzed using SPSS-16 software. Deciduous molar teeth in all four classes showed variability in the number of roots and root canals, and also differed in mean root length and angulation. Type I and IV root canal configurations were observed in the samples, and different types of curvature were recorded for the root canals in all four classes. As deciduous molar teeth exhibit morphologic differences from permanent teeth, a thorough knowledge of the root canals in the former can improve the outcome of pulp treatment.

Comparison of the salivary immunoglobulin concentration levels between children with early childhood caries and caries-free children.

BACKGROUND: Early Childhood Caries (ECC) is one of the most common chronic childhood diseases. In spite of the global decrease in dental caries in the past decades, ECC has become a significant problem in many developing countries and also in a few industrialized nations. Saliva as a host factor can play an important role in the process of dental caries. OBJECTIVE: The aim of this study was to compare sIgA and IgG as saliva components between ECC and caries-free groups. METHODS: In this cross-sectional study, samples of unstimulated saliva of 90 children (45 in ECC group & 45 in caries-free group) were taken with Scully method. Then the concentration levels of sIgA and IgG were measured with Enzyme Linked Immunosorbent Assay and Single Radial Immunodiffusion methods. RESULTS: Mean concentration levels of salivary sIgA and IgG were significantly higher among children with ECC (p<0.05). There was also a weak inverse correlation between sIgA level and DMFT index in ECC group but it was not statistically significant (p=0.056). CONCLUSION: The high concentration of salivary immunoglobulin in children with ECC may be associated with an increased antigenic load, leading to high production of antibodies.