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Anodization is a routine industrial galvanic method that produces a titanium oxide layer on the surface of titanium. Considering the possibility that this technique could influence microbial adsorption and colonization, this

This study evaluated antimicrobial activity of atorvastatin, pravastatin, rosuvastatin, and simvastatin against oral bacteria, and the interaction of simvastatin with standard antimicrobials (amoxicillin and metronidazole).Minimal inhibitory concentration assays were performed with Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Actinomyces odontolyticus, Streptococcus oralis, Streptococcus mitis, Streptococcus salivarius, Streptococcus sanguinis, and Streptococcus gordonii; checkerboard microdilution assays between simvastatin and standard antimicrobials; monospecies and multispecies biofilms.Simvastatin showed the best antimicrobial activity against most species (MIC range from 3.12 to 25 μg/ml), highlighting the sensitivity of P. gingivalis. In the checkerboard assay, synergistic interaction was found between simvastatin and amoxicillin against S. oralis and S. sanguinis. P. gingivalis biofilm was inhibited by simvastatin at 10 and 50× Minimal inhibitory concentration, with similar effects to metronidazole. For multispecies biofilm, SMV reduced the biofilm metabolic activity (79%) and total counts (87%), comparable to amoxicillin. Simvastatin also reduced bacterial counts of Veilonnella parvula, P. gingivalis, Streptococcus mutans, Actinomyces naeslundii, P. intermedia, and Capnocytophaga ochracea in the multispecies biofilm.Simvastatin showed antimicrobial and antibiofilm activity against oral bacteria and may contribute to the control of dysbiosis, and may be considered in clinical studies as an adjuvant in the treatment of periodontitis.

To evaluate propolis type-3 mouthrinse effects on the concentration of volatile sulfur compounds (VSCs) and on tongue dorsum microbial profile. A three-step double-blind, crossover, randomized study with 10 individuals divided into three groups: I-placebo (P); II-ethanolic extract of propolis type-3 3% (EEP); and III-chlorhexidine 0.12% (CHX) and instructed to rinse twice daily for 5 days. Each experimental period was followed by a 21-day washout interval. Morning mouth breath was assessed by VSC concentrations and microbiological samples were obtained from tongue dorsum at baseline and the end of period of rinses and analyzed using checkerboard DNA–DNA hybridization technique for 39 bacterial species. CHX and EEP presented the lowest VSC concentration when compared with placebo (p 0.05). A positive correlation was observed between decrease of bacterial counts and decrease of VCSs concentration for the EEP and CHX. The use of a 3% propolis type-3 mouthrinse is an effective way to prevent morning bad breath. Thus, propolis may be a promising agent for the treatment of halitosis. Propolis type-3 may be used as adjuvant treatment for morning breath malodor.

Objectives The aim of this in vitro study was to incorporate two anti-caries agents, Apigenin and tt-Farnesol, to resin composite and resin cement to reduce the virulence of Streptococcus mutans around dental restorations. Methods Apigenin (Api, 5 mM) and tt-Farnesol (Far, 5 mM) were added alone, together, and combined with fluoride (F). Biofilm of S. mutans was grown on composite discs, and the dry-weight, bacterial viability, and the polysaccharides (alkali-soluble, intracellular and water-soluble) were quantified. CLSM images of the S. mutans biofilm were obtained after three years of water-storage. The effect of the additions on the physicochemical properties and the composite colorimetric parameters were also analyzed. Results The additions did not affect bacterial viability. Api alone and combined with Far or combined with Far and F decreased the bacterial dry-weight, alkali-soluble and intracellular polysaccharides. After three years, the composites containing the additions presented a greater EPS matrix on the top of biofilm. Statistical difference was obtained for the degree of conversion; however, the maximum polymerization rate and curing kinetics were unaffected by the additions. No difference was observed for the water-soluble polysaccharides, flexural strength, and elastic modulus. Api increased the yellowness of the composites. Significance Api, alone and combined, reduced the expression of virulence of S. mutans without jeopardizing the physicochemical properties of the composites.

Purpose/objectives To investigate dental students’ perceptions and concerns regarding the COVID‐19 pandemic, their coping strategies and support resources, and their perceived stress levels. Methods A customized 19‐item survey and the perceived stress scale (PSS) were applied to undergraduate dental students from the US, Spain, Ireland, Chile, India, and Brazil between April 10 and July 5, 2020. Linear modeling and mediation analysis were used to explore the relationships among demographics, stressors, coping mechanisms, social support, and stress Results A total of 4475 students responded to the survey. The majority (72.4%) were women, and 52.3% had no COVID‐19 training at the time of the survey. The students reported that they had to accommodate to changes in patient care (96.6%) and didactic learning (95.2%) activities, while 88.5% of the respondents indicated at least one of their courses moved online. Transition to online courses went “smoothly with some troubles” for 51.8% of the respondents, and 48.3% perceived the faculty as prepared for the online transition; however, 45.9% reported feeling extremely concerned about the impact of COVID‐19 on their education. The average PSS score was 21.9 of 40 (moderate stress). Multivariate models were built for participants with full data (n = 3899). Being male, having completed more dental coursework, and perceiving a smoother transition were associated with lower PSS scores; more concern about academic progress was associated with higher PSS. Faculty support mediated the relationship between a smoothness of transition and concern about academic progress and PSS scores Conclusion Stress caused by the pandemic may be alleviated by smoother transition and good faculty support.

Objective This study evaluated the metabolic activity of hydro-carbon-oxo-borate complex (HCOBc) on a multispecies subgingival biofilm as well as its effects on cytotoxicity. Materials and methods The subgingival biofilm with 32 species related to periodontitis was formed in the Calgary Biofilm Device (CBD) for 7 days. Two different therapeutic schemes were adopted: (1) treatment with HCOBc, 0.12% chlorhexidine (CHX), and negative control group (without treatment) from day 3 until day 6, two times a day for 1 min each time, totaling 8 treatments and (2) a 24-h treatment on a biofilm grown for 6 days. After 7 days of formation, biofilm metabolic activity was determined by colorimetry assay, and bacterial counts and proportions of complexes were determined by DNA-DNA hybridization. Both substances’ cytotoxicity was evaluated by cell viability (XTT assay) and clonogenic survival assay on ovary epithelial CHO-K1 cells and an osteoblast precursor from calvaria MC3T3-E1 cells. Results The first treatment scheme resulted in a significant reduction in biofilm’s metabolic activity by means of 77% by HCOBc and CHX treatments versus negative control. The total count of 11 and 25 species were decreased by treatment with hydro-carbon-oxo-borate complex and CHX, respectively, compared with the group without treatment (p < 0.05), highlighting a reduction in the levels of Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Fusobacterium periodontium. CHX significantly reduced the count of 10 microorganisms compared to the group treated with HCOBc (p < 0.05). HCOBc and CHX significantly decreased the pathogenic red-complex proportion compared with control-treated biofilm, and HCOBc had even a more significant effect on the red complex than CHX had (p ≤ 0.05). For the second treatment scheme, HCOBc complex and CHX significantly decreased 61 and 72% of control biofilms’ metabolic activity and the counts of 27 and 26 species, respectively. HCOBc complex did not significantly affect the proportions of formed biofilms, while CHX significantly reduced red, orange, and yellow complexes. Both substances exhibited similar cytotoxicity results. Conclusions This short communication suggested that the HCOBc complex reduced a smaller number of bacterial species when compared to chlorhexidine during subgingival biofilm formation, but it was better than chlorhexidine in reducing red-complex bacterial proportions. Although HCOBc reduced the mature 6-day-old subgingival multispecies biofilms, it did not modify bacterial complexes’ ratios as chlorhexidine did on the biofilms mentioned above. Future in vivo studies are needed to validate these results. Clinical relevance HCOBc complex could be used to reduce red-complex periodontal bacterial proportions.

The development of oral biofilm models has been extremely important to study the specific role of most microbial species at the early stages of periodontitis. The current knowledge on monospecies or multispecies biofilms originates mainly from the observation of in vitro dynamic or static biofilm model systems, which were engineered to mimic clinical oral conditions. In the last few decades, mounting evidence has confirmed that biofilms are the major form of bacterial lifestyle, and more importantly, that microorganisms dwelling in sessile mixed-species aggregates display completely different phenotypes and physiological characteristics than when living in planktonic pure cultures. Interspecies interactions within these communities, mediated by chemical communication systems, have been shown to affect biofilm physiology and increase antimicrobial resistance by up to 1000 fold. These aspects reinforce the importance of developing multispecies biofilm models to better understand and control biofilms. Literature reports demonstrate that while monospecies models are still most commonly used in caries research, authors have used different multispecies models to study periodontal diseases. Periodontitis is a polymicrobial biofilm-dependent disease mainly associated with Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Interestingly, these species hardly adhere to substrates commonly used for biofilm formation, which makes multispecies models essential for an accurate analysis of periodontitis-related biofilms. The multispecies models currently available are generally composed of 6-10 species, but a more recent 34-species model was developed to better examine the dynamics within oral biofilms. The complexity of such polymicrobial biofilm models mimics more consistently the oral microbiome and different aspects of the oral environment. Collectively, the evidence on multispecies biofilm models described herein may support future studies on the use of antimicrobials for biofilm control as well as provide research opportunities to expand the current knowledge on interspecies interactions. The present manuscript reviews the most recent updates on in vitro biofilm model systems for periodontitis.

This study aimed to validate an in vitro periodontal biofilm model with complex subgingival microbial communities grown in a stirred bioreactor. Experimental biofilms were characterized and examined for their growth kinetics over time. After incubation under anaerobic conditions for 3 days, biofilm cultures formed on the substrate were collected and analyzed. The specific growth rate in the exponential phase was estimated to be 0.3915 h−1, with no significant differences in growth kinetics and CFU counts between the replicates (P > 0.05). The biofilm architecture was consistent in each time-point, with bacterial cells presenting different morphology and completely colonizing the cementum surface. To conclude, the three-day subgingival biofilm model developed in our study successfully mimicked the growth of complex microbial communities.

The objective was to test the influence of a pulsed electromagnetic field (PEMF) on bacterial biofilm colonization around implants incorporated with healing abutments. Healing abutments with (test ...

The objective of this work was to develop a subgingival biofilm model using a stirred bioreactor. Discs of bovine teeth were adapted to a stirred bioreactor filled with a culture medium containing bacterial species associated with periodontal health or disease. After anaerobic incubation, the biofilms growing on the substratum surfaces were collected and analyzed. The mean number of Colony-forming Units (CFUs) varied, but with no difference between 3 and 7 days of biofilm formation (

Made available in DSpace on 2020-12-12T02:22:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-10 Plant-derived compounds incite applications virtually on every biomedical field due to the expedient antioxidant, anti-inflammatory and antimicrobial properties in conjunction with a natural character. Here, quercetin (QCT), a flavonoid with therapeutic potentials relevant to the oral environment, was encapsulated within metal-organic frameworks (MOFs) to address the concept of on-demand release of phytochemicals at the biointerface. We verified the applicability of a microporous MOF (ZIF-8) as a controlled-release system for QCT, as well as investigated the incorporation of QCT@ZIF-8 microparticles into a dental adhesive resin for desirable therapeutic capabilities at the tooth-restoration interface. QCT was encapsulated within the frameworks through a water-based, one-step synthetic process. The resulting QCT@ZIF-8 microparticles were characterized with respect to chemical composition, crystal structure, thermal behavior, micromorphology, and release profile under acidic and physiological conditions. A model dental adhesive formulation was enriched with the bioactive microparticles; both the degree of conversion (DC) of methacrylic double bonds and the polymer thermal behavior were accounted for. The results confirm that crystalline QCT@ZIF-8 microparticles with attractive loading capacities, submicron sizes, high thermal stability and responsiveness to environmental pH change were successfully manufactured. The concentration of QCT@ZIF-8 in the resin system was a key factor to maintain an optimal DC plateau and rate of polymerization. Essentially, one-step encapsulation of QCT in biocompatible ZIF-8 matrices can be easily achieved, and QCT@ZIF-8 microparticles proved as smart platforms to carry bioactive compounds with potential use to prevent microbial and enzymatic degradation of hard tissues and extracellular matrix components. Department of Physics School of Sciences São Paulo State University (UNESP) Department of Chemistry School of Sciences São Paulo State University (UNESP) Department of Restorative Dentistry College of Dentistry University of Illinois at Chicago (UIC) Dental Research Division Guarulhos University (UNG) Department of Inorganic Chemistry Institute of Chemistry São Paulo State University (UNESP) Department of Physics School of Sciences São Paulo State University (UNESP) Department of Chemistry School of Sciences São Paulo State University (UNESP) Department of Inorganic Chemistry Institute of Chemistry São Paulo State University (UNESP)

Background The 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions grouped the diseases previously recognized as chronic (CP) or aggressive (AgP) periodontitis under a single category named periodontitis. The rationale for this decision was the lack of specific patterns of immune-inflammatory response or microbial profiles associated with CP or AgP. However, no previous studies have compiled the results of all studies comparing subgingival microbial data between these clinical conditions. Thus, this systematic review aimed to answer the following focused question: "Do patients with AgP periodontitis present differences in the subgingival microbiota when compared with patients with CP?" Methods A systematic review was conducted according to the PRISMA statement. The MEDLINE, EMBASE, and Cochrane databases were searched up to June 2019 for studies of any design (except case reports, case series, and reviews) comparing subgingival microbial data from patients with CP and AgP. Results A total of 488 articles were identified and 56 were included. Thirteen studies found Aggregatibacter actinomycetemcomitans elevated in AgP in comparison with CP, while Fusobacterium nucleatum, Parvimonas micra, and Campylobacter rectus were elevated in AgP in a few studies. None of these species were elevated in CP. However, the number of studies not showing statistically significant differences between CP and AgP was always higher than that of studies showing differences. Conclusion These results suggested an association of A. actinomycetemcomitans with AgP, but neither this species nor the other species studied to date were unique to or could differentiate between CP and AgP (PROSPERO #CRD42016039385).

This study compared the gene expression of the immunoinflammatory markers interleukin (IL)-6, IL-1&szlig, and tumor necrosis factor alpha (TNF-&alpha, ), the matrix metalloproteinases (MMP)-1, -2, -8, and -9, and the tissue inhibitors of matrix metalloproteases (TIMP)-1 and -2 in the gingival tissue of individuals with periodontal and peri-implant disease. The study population included individuals with four periodontal statuses: periodontal health (PH group, n = 20), periodontitis (P group, n = 20), peri-implant health (PIH group, n = 20), and peri-implantitis (PI group, n = 20). Gingival biopsies were collected from one tooth per patient according to the inclusion criteria of each group. The mRNA levels of IL-6, IL-1&szlig, TNF-&alpha, MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were evaluated by qPCR. The levels of IL-1&szlig, were significantly higher in the PI group when compared to the other groups (p &lt, 0.05), while the levels of IL-6 were significantly higher in the groups with periodontal and peri-implant disease when compared with the healthy groups (p &lt, 0.05), however, the levels of IL-6 did not differ between the PI and P groups (p &gt, 0.05). For all other studied biomarkers, no significant differences were observed between groups (p &gt, 0.05). IL-6 and IL-1&szlig, presented higher levels of mRNA in diseased periodontal and peri-implant tissues. However, the expression of metalloproteinases and their inhibitors did not differ between the different periodontal statuses.

The objective was to test the influence of a pulsed electromagnetic field (PEMF) on bacterial biofilm colonization around implants incorporated with healing abutments. Healing abutments with (test group) and without (control group) active PEMF devices were placed in a multispecies biofilm consisting of 31 different bacterial species. The biofilm composition and total bacterial counts (x10

Ethnopharmacological relevance Propolis has been used in folk medicine for thousands of years and, in the past few decades, it has attracted renewed interest. Although propolis has been traditionally used in many communities worldwide against parasitic diseases, its effect against Schistosoma mansoni infection remains unclear. Aim of the study To demonstrate the effects of Brazilian red propolis on Schistosoma mansoni ex vivo and in an animal model of schistosomiasis. Materials and methods In vitro, we monitored phenotypic and tegumental changes as well as the effects of the crude extract of propolis on pairing and egg production. In a mouse infected with either immature (early infection) or adult (chronic infection) worms, propolis was administered by oral gavage and we studied the influence of this natural product on worm burden and egg production. Results Propolis 25 μg/mL reduced motility and caused 100% mortality of adult parasites ex vivo. Further analysis revealed a pronounced reduction in oviposition after exposure to propolis at sub-lethal concentrations. In addition, scanning electron microscopy showed morphological alterations in the tegument of schistosomes. In the animal model, propolis markedly reduced worm burden and egg production in both early and chronic S. mansoni infection when compared to untreated control animals. Conclusions The efficacy of Brazilian red propolis in both in vitro and in vivo studies suggests its potential anthelmintic properties against S. mansoni infection.

This study investigated the effects of Brazilian Red Propolis (BRP) extract on seven-day-old multispecies subgingival biofilms. Mixed biofilm cultures containing 31 species associated with periodontal health or disease were grown for six days on a Calgary device. Then, mature biofilms were treated for 24 h with BRP extract at different concentrations (200&ndash, 1600 &micro, g/mL), amoxicillin (AMOXI) at 54 &micro, g/mL (positive control) or vehicle (negative control). Biofilm metabolic activity was determined by colorimetry, and bacterial counts/proportions were determined by DNA&ndash, DNA hybridization. Data were analyzed by Kruskal&ndash, Wallis and Dunn&rsquo, s tests. Treatment with BRP at 1600, 800 and 400 &mu, g/mL reduced biofilm metabolic activity by 56%, 56% and 57%, respectively, as compared to 65% reduction obtained with AMOXI. Mean total cell counts were significantly reduced in all test groups (~50&ndash, 55%). Lower proportions of red, green and yellow complex species were observed upon treatment with BRP (400 &micro, g/mL) and AMOXI, but only AMOXI reduced the proportions of Actinomyces species. In conclusion, BRP extract was as effective as AMOXI in killing seven-day-old multispecies biofilm pathogens and did not affect the levels of the host-compatible Actinomyces species. These data suggest that BRP may be an alternative to AMOXI as an adjunct in periodontal therapy. In vivo studies are needed to validate these results.

Previously, we demonstrated the anti-inflammatory properties of vestitol in a neutrophil model. Here, we show the effects of vestitol on macrophage activation and function. Vestitol was obtained from Brazilian red propolis after bioguided fractionation and tested at different concentrations in LPS-activated RAW 264.7 murine macrophages for nitric oxide (NO) production and cell viability. The levels of TNF-α, IL1-β, TGF-β, IL-4, IL-6, IL-10, IL-12, GM-CSF, IFN-ɣ and gene expression related to cytokines, NO, PI3K-AKT and signal transduction pathways were assayed by ELISA and RT-qPCR, respectively. Differences were determined by one-way ANOVA followed by Tukey-Kramer. Vestitol inhibited NO production by 83% at 0.55 μM without affecting cell viability when compared to the vehicle control (P < 0.05). Treatment with vestitol reduced GM-CSF, IL-6, TNF-α, IL-4 and TGF-β levels and increased IL-10 release (P < 0.05). Vestitol affected the expression of genes related to NF-κB pathway, NO synthase, and inhibition of leukocyte transmigration, namely: Ccs, Ccng1, Calm1, Tnfsf15, Il11, Gata3, Gadd45b, Cdkn1b, Csf1, Ccl5, Birc3 (negatively regulated), and Igf1 (positively regulated). Vestitol diminished the activation of NF-κB and Erk 1/2 pathways and induced macrophages into M2-like polarization. The modulatory effects of vestitol are due to inhibition of NF-κB and Erk 1/2 signaling pathways, which are associated with the production of pro-inflammatory factors.

A taxa de sucesso endodôntico varia entre 86% e 98%, mas para que esses valores sejam atingidos, é fundamental a remoção de todo e qualquer tipo de microrganismos do canal radicular. Para alcançar o sucesso do tratamento a longo prazo, é necessária uma excelente desinfecção endodontica. Durante o manejo, a instrumentação é fundamental, porém, sozinha não promove eliminação completa das bactérias, assim surge a importância das substâncias antimicrobianas para eliminação dos microrganismos. Atualmente, temos como principais irrigantes endodônticos o Hipoclorito de sódio (NaOCl) e a Clorexidina (CHX), mas, apesar de muito utilizados, podem ser tóxicos e prejudiciais aos tecidos periapicais. Diversas substâncias estão sendo pesquisadas a fim de encontrarem a solução antimicrobiana ideal e uma delas é a própolis. Portanto, o objetivo do presente trabalho é avaliar a eficácia da própolis na desinfecção do canal radicular, quando comparada a CHX e o NaOCl, por meio da literatura. A própolis coletada das plantas pelas abelhas, é uma substância resinosa e biocompatível, além de ter propriedades antibacterianas, anti-inflamatórias, antitumorais, antifúngicas etc. Baseado nos artigos levantados, observou-se que a espécie Enterococcus faecalis destacou-se como principal patógeno responsável pelo insucesso do tratamento endodôntico. Pesquisas mostram que a própolis mostrou efetividade contra a Candida Albicans, Enterococcus faecalis, Staphylococcus aureus, Prevotella e Actinomyces, em diferentes formas de pesquisas. Com base nesse estudo concluímos que a própolis, apesar de não ser o agente irrigante com maior efetividade em comparação aos demais, vem despertando interesse nas pesquisas por ser uma solução que apresenta ótimos resultados contra microrganismos endodônticos.

Objetivo: realizar um ensaio in vitro de microdureza em diferentes materiais restauradores. Metodos: Para cada material restaurador (FUJI IX - Cimento de Ionomero de Vidro; Tetric - resina composta convencional; Beautifil II; resina composta bioativa) foram confeccionadas 10 restauracoes em dentes incisivos bovinos, cavitados por uma ponta diamantada 2092 KG Sonrensen, seguindo as recomendacoes de cada fabricante. O ensaio de microdureza foi realizado em diferentes profundidades (superficie, 0.4mm, 1.0mm, 2.0mm, 3.0mm e 4.0mm) e em dois momentos, imediatamente e 24h apos a fotoativacao. Os dados foram analisados pelo teste de analise de variância (ANOVA) e teste Tukey. Resultados: As medias de microdureza diminuiram significativamente com o aumento da profundidade, com valores mais baixos no primeiro momento avaliado. A resina composta bioativa apresentou as maiores medias de microdureza. Conclusao: os materiais testados apresentaram diminuicao gradual da microdureza com o aumento da profundidade, sendo mais acentuada em profundidades acima de 2.0mm. Em todos os materiais restauradores, as medias de microdureza mais altas foram registradas 24 horas apos a fotoativacao. A resina composta bioativa apresentou os melhores resultados nas diferentes profundidades avaliadas.

Por milhares de anos a própolis tem sido utilizada na medicina popular e, em estudos recorrentes, apresentando cada vez mais aplicações. Considerando a atenção que o sistema de patentes tem recebido nas últimas décadas instigando a inovação tecnológica por parte de empresas e instituições de pesquisa, torna-se vultoso o levantamento de dados acerca dos depósitos de patentes envolvendo a própolis. O presente estudo prospectivo avaliou aspectos quantitativos do depósito de patentes registrados em bases de dados internacionais e nacionais entre os anos 2000 e 2020. Na última década, com pico em 2012, houve um aumento no número de pedidos de patentes. A maioria dos registros são oriundos da Ásia, em especial da China, Coreia do Sul e Japão, com 1845, 584 e 222 pedidos de patente, respectivamente. Com 102 depósitos de patentes, o Brasil ocupa a quarta posição, sendo que 48% estão vinculadas às universidades, enquanto 12% estão envolvidos com empresas. No que concerne a aplicabilidade da própolis, os mais frequentes são para fins médicos, odontológicos e higiênicos (1504 patentes), seguido do setor de alimentos ou bebidas não alcoólicas e conservantes (964). Em conjunto, os resultados desse estudo mostram o avultado interesse mundial da indústria e da academia pelos benefícios própolis.

Improving the effects of chemotherapy and reducing the side effects are important goals in cancer research. Various approaches have been examined to enhance the effectiveness of chemotherapy. For example, signal transduction inhibitors or hormonal based approaches have been included with chemo- or radio-therapy. MIA-PaCa-2 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells both express the estrogen receptor (ER). The effects of β-estradiol on the growth of PDAC cells has not been examined yet the ER is expressed in PDAC cells. We have examined the effects of combining β-estradiol with chemotherapeutic drugs, signal transcription inhibitors, natural products and nutraceuticals on PDAC. In most cases, inclusion of β-estradiol with chemotherapeutic drugs increased chemosensitivity. These results indicate some approaches involving β-estradiol which may be used to increase the effectiveness of chemotherapeutic and other drugs on the growth of PDAC.

To evaluate propolis type-3 mouthrinse effects on the concentration of volatile sulfur compounds (VSCs) and on tongue dorsum microbial profile.A three-step double-blind, crossover, randomized study with 10 individuals divided into three groups: I-placebo (P); II-ethanolic extract of propolis type-3 3% (EEP); and III-chlorhexidine 0.12% (CHX) and instructed to rinse twice daily for 5 days. Each experimental period was followed by a 21-day washout interval. Morning mouth breath was assessed by VSC concentrations and microbiological samples were obtained from tongue dorsum at baseline and the end of period of rinses and analyzed using checkerboard DNA-DNA hybridization technique for 39 bacterial species.CHX and EEP presented the lowest VSC concentration when compared with placebo (p 0.05). Even in the absence of mechanical plaque control, CHX and EEP treatments reduced VSC levels and there were no statistical differences for VSC measurement between CHX and EEP. There was a significant reduction in mean counts of 10 species including some VSC producers (Prevotella intermedia, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) by EEP. Total counts of organisms, gram-negative and gram-positive bacterial species showed a decrease for EEP and CHX (p 0.05). In addition, no statistical difference was observed between EEP and CHX (p 0.05). A positive correlation was observed between decrease of bacterial counts and decrease of VCSs concentration for the EEP and CHX.The use of a 3% propolis type-3 mouthrinse is an effective way to prevent morning bad breath. Thus, propolis may be a promising agent for the treatment of halitosis.Propolis type-3 may be used as adjuvant treatment for morning breath malodor.

This study investigated the antimicrobial effects of the ethanolic extract of Brazilian red propolis (BRP) on multispecies biofilms. A seven-day-old subgingival biofilm with 32 species was grown in a Calgary device. Biofilms were treated with BRP (1,600, 800, 400 and 200 μg ml

Periodontopathogenic subgingival biofilm is the main etiological agent of periodontitis. Thus, a search for antimicrobials as adjuvant for periodontal treatment in the literature is intense. Cetylpyridinium chloride (CPC) is a well-known antimicrobial agent commonly used in mouthrinses. However, CPC effects on a complex biofilm model were not found over the literature. Therefore, the aim of this manuscript is to evaluate 0.075% CPC antimicrobial properties in a multispecies subgingival biofilm model in vitro. The subgingival biofilm composed by 31 species related to periodontitis was formed for 7 days, using the calgary device. The treatments with CPC and chlorhexidine (CHX) 0.12% (as positive control) were performed 2x/day, for 1 min, from day 3 until the end of experimental period, totaling 8 treatments. After 7 days of biofilm formation, biofilm metabolic activity was evaluated by a colorimetric reaction and biofilms microbial composition by DNA-DNA hybridization. Statistical analysis was performed using ANOVA with data transformed via BOX-COX followed by Dunnett post-hoc. Both CPC and CHX reduced biofilm metabolic activity in 60% and presented antimicrobial activity against 13 different species. Specifically, only CHX reduced levels of F.n. vicentii and P. gingivalis while only CPC reduced A. odontolyticus and A. israelli. CPC was as effective as CHX as antimicrobial through in vitro complex multispecies subgingival biofilm. However, future studies using in vivo models of experimental periodontal disease should be performed to prove such effect. Resumo O biofilme subgengival periodontopatogênico é o principal agente etiológico da periodontite. Assim, a pesquisa de antimicrobianos como adjuvantes para o tratamento periodontal na literatura é intensa. Cloreto de cetilpiridínio (CPC) é um agente antimicrobiano comumente usado em enxaguatórios bucais. No entanto não foram encontrados na literatura estudos avaliando os efeitos do CPC em um modelo complexo de biofilme. Portanto, o objetivo deste artigo é avaliar as propriedades antimicrobianas do cloreto de cetilpiridinio 0,075% em um modelo de biofilme subgengival multiespécie in vitro. O biofilme subgengival composto por 31 espécies relacionadas à periodontite foi formado por 7 dias, utilizando o dispositivo calgary. Os tratamentos com CPC e clorexidina (CHX) 0,12% (controle positivo) foram realizados 2x/dia, por 1 min, do dia 3 até o final do período experimental, totalizando 8 tratamentos. Após 7 dias de formação do biofilme, a atividade metabólica do biofilme foi avaliada por reação colorimétrica e a composição microbiana dos biofilmes por hibridização DNA-DNA. A análise estatística foi realizada usando ANOVA com dados transformados via BOX-COX seguido do teste de Dunnett. Tanto o CPC como a CHX reduziram a atividade metabólica do biofilme em aproximadamente 60% e apresentaram atividade antimicrobiana contra 13 espécies diferentes. Especificamente, apenas os níveis de F.n. Vicentii e P. gingivalis foram reduzidos somente pelo tratamento com a CHX enquanto apenas o CPC reduziu A. odontolyticus e A. israelli. O CPC foi tão eficaz quanto o CHX como antimicrobiano através de biofilme subgengival complexo multiespecífico in vitro. No entanto, futuros estudos usando modelos in vivo de doença periodontal experimental devem ser realizados para comprovar tal efeito.

Pancreatic cancer is devastating cancer worldwide with few if any truly effective therapies. Pancreatic cancer has an increasing incidence and may become the second leading cause of death from cancer. Novel, more effective therapeutic approaches are needed as pancreatic cancer patients usually survive for less than a year after being diagnosed. Control of blood sugar levels by the prescription drug metformin in diseases such as diabetes mellitus has been examined in association with pancreatic cancer. While the clinical trials remain inconclusive, there is hope that certain diets and medications may affect positively the outcomes of patients with pancreatic and other cancers. Other natural compounds may share some of the effects of metformin. One “medicinal” fruit consumed by millions worldwide is berberine (BBR). Metformin and BBR both activate AMP-activated protein kinase (AMPK) which is a key mediator of glucose metabolism. Glucose metabolism has been shown to be very important in cancer and its significance is increasing. In the following studies, we have examined the effects of metformin, BBR and a panel of modified BBRs (NAX compounds) and chemotherapeutic drugs on the growth of four different human pancreatic adenocarcinoma cell lines (PDAC). Interestingly, the effects of metformin could be enhanced by BBR and certain modified BBRs. Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53. Certain NAX compounds may interact with WT-TP53 and metformin treatment to alter the expression of key molecules involved in cell growth. These results suggest a therapeutic approach by combining certain pharmaceutical drugs and nutraceuticals to suppress the growth of cancer cells.

Mutations at the TP53 gene are readily detected (approximately 50–75%) in pancreatic ductal adenocarcinoma (PDAC) patients. TP53 was previously thought to be a difficult target as it is often mutated, deleted or inactivated on both chromosomes in certain cancers. In the following study, the effects of restoration of wild-type (WT) TP53 activity on the sensitivities of MIA-PaCa-2 pancreatic cancer cells to the MDM2 inhibitor nutlin-3a in combination with chemotherapy, targeted therapy, as well as, nutraceuticals were examined. Upon introduction of the WT-TP53 gene into MIA-PaCa-2 cells, which contain a TP53 gain of function (GOF) mutation, the sensitivity to the MDM2 inhibitor increased. However, effects of nutlin-3a were also observed in MIA-PaCa-2 cells lacking WT-TP53, as upon co-treatment with nutlin-3a, the sensitivity to certain inhibitors, chemotherapeutic drugs and nutraceuticals increased. Interestingly, co-treatment with nutlin-3a and certain chemotherapeutic drug such as irinotecan and oxaliplatin resulted in antagonistic effects in cells both lacking and containing WT-TP53 activity. These studies indicate the sensitizing abilities that WT-TP53 activity can have in PDAC cells which normally lack WT-TP53, as well as, the effects that the MDM2 inhibitor nutlin-3a can have in both cells containing and lacking WT-TP53 to various therapeutic agents.