Reveals of quercetin's therapeutic effects on oral lichen planus based on network pharmacology approach and experimental validation.

Oral lichen planus (OLP) is a localized autoimmune disease of the oral mucosa, with an incidence of up to 2%. Although corticosteroids are the first-line treatment, they cause several adverse effects. Quercetin, a naturally occurring compound, has fewer side-effects and provides long-term benefits. Besides, it has powerful anti­inflammatory activities. Here, we combined network pharmacology with experimental verification to predict and verify the key targets of quercetin against OLP. First, 66 quercetin-OLP common targets were analyzed from various databases. The protein-protein interaction (PPI) network was constructed. Topology analysis and MCODE cluster analysis of common targets were conducted to identify 12 key targets including TP53, IL-6 and IFN-γ and their connections. Gene functions and key signaling pathways, including reactive oxygen species metabolism, IL-17 pathway and AGE-RAGE pathway, were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, in vitro experiments showed that quercetin interfered with Th1/Th2 balance by acting on IL-6 and IFN-γ to modulate the immune system in treating OLP. Quercetin considerably affected the apoptosis and migration of T lymphocytes in OLP patients. Our study reveals the potential therapeutic targets and signaling pathways of quercetin associated with OLP, and establishes the groundwork for future clinical applications.

Development and Evaluation of Thermosensitive Hydrogels with Binary Mixture of Scutellariae baicalensis radix Extract and Chitosan for Periodontal Diseases Treatment.

Scutellaria baicalensis root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of S. baicalensis radix lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with S. baicalensis radix lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of S. baicalensis radix lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of S. baicalensis radix extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.

The effect of caffeic acid phenethyl ester and Ankaferd Blood Stopper on the diabetic and nondiabetic gingival wound healing: an experimental study

Background/aim: Healthy wound healing is very important for patient comfort. Diabetes is one of the factors that negatively affect wound healing. Ankaferd Blood Stopper (ABS) and caffeic acid phenethyl ester (CAPE) are antiinflammatory and antimicrobial agents and may have positive effects on wound healing. Materials and methods: In this study, 72 male Wistar albino rats were used. Rats; control, CAPE, ABS, diabetes + control, diabetes + ABS and diabetes + CAPE groups were divided into 6 groups. A healthy 36 rats created diabetes using streptozotocin (STZ). A gingival wound was created using a 4-mm punch biopsy in the gingival tissue under the lower anterior incisors of the rats. Results: The comparison between the nondiabetic groups had a statistically significant positive effect compared to the control group of CAPE and ABS (P ˂ 0.05). In the comparison between ABS and diabetes + ABS groups and in the comparison between CAPE and diabetes + CAPE groups, a decrease in vascularization in diabetes + CAPE groups was observed and it was statistically significant (P ˂ 0.005). Conclusion: ABS and CAPE have been found to have positive effects on gingival wound healing in the nondiabetic group. We think that this situation is caused by its antiinflammatory and antimicrobial properties.

In search of preventive strategies: novel high-CBD Cannabis sativa extracts modulate ACE2 expression in COVID-19 gateway tissues.

With the current COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. The inhibition of viral entry and thus spread is a plausible therapeutic avenue. SARS-CoV-2 uses receptor-mediated entry into a human host via the angiotensin-converting enzyme 2 (ACE2), which is expressed in lung tissue as well as the oral and nasal mucosa, kidney, testes and gastrointestinal tract. The modulation of ACE2 levels in these gateway tissues may be an effective strategy for decreasing disease susceptibility. Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. However, its effects on ACE2 expression remain unknown. Working under a Health Canada research license, we developed over 800 new C. sativa cultivars and hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues. Using artificial 3D human models of oral, airway and intestinal tissues, we identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels. Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells. While our most effective extracts require further large-scale validation, our study is important for future analyses of the effects of medical cannabis on COVID-19. The extracts of our most successful novel high-CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.

Protective Effects of N-Acetylcysteine against Radiation-Induced Oral Mucositis In Vitro and In Vivo.

PURPOSE: Radiation-induced oral mucositis limits delivery of high-dose radiation to targeted cancers. Therefore, it is necessary to develop a treatment strategy to alleviate radiation-induced oral mucositis during radiation therapy. We previously reported that inhibiting reactive oxygen species (ROS) generation suppresses autophagy. Irradiation induces autophagy, suggesting that antioxidant treatment may be used to inhibit radiation-induced oral mucositis. MATERIALS AND METHODS: We determined whether treatment with N-acetyl cysteine (NAC) could attenuate radiation-induced buccal mucosa damage in vitro and in vivo. The protective effects of NAC against oral mucositis were confirmed by transmission electron microscopy and immunocytochemistry. mRNA and protein levels of DNA damage and autophagy-related genes were measured by quantitative real-time polymerase chain reaction and western blot analysis, respectively. RESULTS: Rats manifesting radiation-induced oral mucositis showed decreased oral intake, loss of body weight, and low survival rate. NAC intake slightly increased oral intake, body weight, and the survival rate without statistical significance. However, histopathologic characteristics were markedly restored in NAC-treated irradiated rats. LC3B staining of rat buccal mucosa revealed that NAC treatment significantly decreased the number of radiation-induced autophagic cells. Further, NAC inhibited radiation-induced ROS generation and autophagy signaling. In vitro, NAC treatment significantly reduced the expression of NRF2, LC3B, p62, and Beclin-1 in keratinocytes compared with that after radiation treatment. CONCLUSION: NAC treatment significantly inhibited radiation-induced autophagy in keratinocytes and rat buccal mucosa and may be a potentially safe and effective option for the prevention of radiation-induced buccal mucosa damage.

Hybrid nanofilms as topical anesthetics for pain-free procedures in dentistry.

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are related to hydrophilic and low mucoadhesive forms. Therefore, we have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine-prilocaine (LDC-PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The most appropriate hybrid nanofilm combined the advantages of both pectin (PCT) and NLC components. The resultant material presented sustained LDC-PLC release profile for more than 8 h; permeation across porcine buccal mucosa almost twice higher than control and non-cytotoxicity against 3T3 and HACAT cell lines. Then, the in vivo efficacy of PCT/NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longest-lasting anesthetic effect (> 7 h), assessed by tail flick test in mice. These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry.

The efficacy of an ayurvedic preparation of yashtimadhu (Glycyrrhiza glabra) on radiation-induced mucositis in head-and-neck cancer patients: A pilot study.

BACKGROUND: Oral mucositis is a common and debilitating painful side effect of many forms of chemotherapy and radiation therapy. Mucositis may lead to dose reductions and unplanned interruptions of chemotherapy and/or radiotherapy (RT) and often affects patients' quality of life. AIM: The objective of the study was to assess the efficacy of the ayurvedic preparation in decreasing the severity of mucositis in head-and-neck cancer patients receiving concomitant chemoradiotherapy. MATERIALS AND METHODS: In this prospective randomized study, the patients were divided into three groups. Group 1 patients received conventional mucositis treatment, whereas Group 2 patients received ayurvedic preparation Yashtimadhu in addition to conventional treatment. Group 3 patients received honey for local application in oral cavity as well as one tea spoon of honey twice daily orally in addition to routine conventional treatment. All the patients were assessed for mucositis at the end of every week during the RT for a period of 6 weeks. RESULTS: A significant difference was observed between the groups at each time point. Nearly 42.85% of patients in conventional treatment arm developed Grade 3 mucositis, 20% of patients developed Grade 3 mucositis in group where honey was given, and only 15.5% of patients developed Grade 3 mucositis in Yastimadhu group. Unplanned treatment breaks and hospitalization of patients were reduced with the use of yashtimadhu as compared to other two groups. CONCLUSION: Yashtimadhu was observed to be effective and delayed the development of severe form of mucositis. The drug appeared to be more efficient in the management of radiation-induced mucositis.

Adjuvanting Allergen Extracts for Sublingual Immunotherapy: Calcitriol Downregulates CXCL8 Production in Primary Sublingual Epithelial Cells.

Application of allergens onto the sublingual epithelium is used to desensitize allergic individuals, a treatment known as sublingual immunotherapy. However, the response of sublingual epithelial cells to house dust mite allergen and potential tolerance-promoting adjuvants such as Toll-like receptor (TLR) ligands and calcitriol has not been investigated. In order to study this, primary sublingual epithelial cells were isolated from dogs and cultured in vitro. After 24-h incubation with a Dermatophagoides farinae extract, a Dermatophagoides pteronyssinus extract, TLR2 ligands (FSL-1, heat-killed Listeria monocytogenes, Pam3CSK4), a TLR3 ligand (poly I:C), a TLR4 ligand [lipopolysaccharide (LPS)], and calcitriol (1,25-dihydroxyvitamin D3), viability of the cells was analyzed using an MTT test, and their secretion of interleukin 6 (IL-6), IL-10, CXCL8, and transforming growth factor ß1 (TGF-ß1) was measured by enzyme-linked immunosorbent assay. Additionally, to evaluate its potential effect as an adjuvant, sublingual epithelial cells were incubated with calcitriol in combination with a D. farinae extract followed by measurement of CXCL8 secretion. Furthermore, the effect of D. farinae and calcitriol on the transcriptome was assessed by RNA sequencing. The viability of the sublingual epithelial cells was significantly decreased by poly I:C, but not by the other stimuli. CXCL8 secretion was significantly increased by D. farinae extract and all TLR ligands apart from LPS. Calcitriol significantly decreased CXCL8 secretion, and coadministration with D. farinae extract reduced CXCL8 concentrations to levels seen in unstimulated sublingual epithelial cells. Although detectable, TGF-ß1 secretion could not be modulated by any of the stimuli. Interleukin 6 and IL-10 could not be detected at the protein or at the mRNA level. It can be concluded that a D. farinae extract and TLR ligands augment the secretion of the proinflammatory chemokine CXCL8, which might interfere with sublingual desensitization. On the other hand, CXCL8 secretion was reduced by coapplication of calcitriol and a D. farinae extract. Calcitriol therefore seems to be a suitable candidate to be used as adjuvant during sublingual immunotherapy.

Efficacy of Improvised Topical Zinc (1%) Ora-Base on Oral Mucositis during Cancer Chemo-Radiation-A Randomized Study.

Oral mucositis refers to erythematous and ulcerative lesions of oral mucosa during chemo/radiotherapy. Treatment modalities were directed towards reduction in severity of oral mucositis. Zinc plays an important role to retard oxidative processes and is considered as the critical component in wound healing. To compare the efficacy of zinc alone with improvised zinc preparation in reducing the severity of oral mucositis. Improvised zinc was a combination of zinc oxide, amla, tulsi and curcumin at 1% therapeutic concentrations. Seventy-five subjects undergoing chemo/radiotherapy were randomly divided into three groups: Group A (25 subjects) had received topical 5% zinc oxide paste trice daily application after food for entire treatment period, initiated 2 d prior to radiotherapy. Group B (25) received improvised zinc preparations (1%) and instructed to apply same as group A. Group C (25) received standard treatment offered by cancer hospital. All the groups were assessed for oral mucositis using WHO grading system at 7th, 14th, 21st, 28th, 35th day by the oncologist and results were tabulated for statistical analysis. Severity of oral mucositis reduced in zinc and improvised zinc group (p=0.096) when compared with controls with significant p value (0.037). Comparison of improvised zinc preparation (1%) group with only zinc group revealed that severity of overall mucositis though was not significant, was less in improvised zinc group with p value (0.029, 0.013) at 28 and 35 d respectively. Improvised zinc administration during radiation therapy was beneficial in reduction of oral mucositis during cancer treatment.

Development and evaluation of mucoadhesive buccal dosage forms of lidocaine hydrochloride by ex-vivo permeation studies.

Intraoral lidocaine formulations are applied in children and adults for pain relief. The potential risks associated with orally administered lidocaine due to accidental ingestions were highlighted in a warning letter by the US Food and Drug Administration (FDA). This increases the urgency for a need of a child-appropriate dosage forms. For risk minimization, a novel buccal composite dosage form was developed consisting of a lidocaine containing minitablet centered on top of a bilayered mucoadhesive buccal film, so called composite. The preparation included direct tableting of minitablets as well as film-casting technique. Within a comparability study, the permeation of this composite was classified against marketed lidocaine gel, a single-layer film, and a minitablet. These ex-vivo permeation studies under physiologically related conditions in combination with LC-MS/MS quantification enabled the evaluation of permeation in clinically relevant short-term application. The composite showed comparable permeation to marketed gel (104.26 ± 30.15 µg/cm2 vs 128.17 ± 12.49 µg/cm2 cumulative amount of drug) and a higher permeation compared to film (25.84 ± 6.01 µg/cm2). Therefore, a controlled drug application can be assumed by the composite, whereby the risk of inadvertent swallowing as well as uncontrolled absorbed amount of drug substance may be substantially minimized.

Daily Time of Radiation Treatment Is Associated with Subsequent Oral Mucositis Severity during Radiotherapy in Head and Neck Cancer Patients.

BACKGROUND: Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer. METHODS: We used electronic medical records of 190 patients with head and neck squamous cell carcinoma who completed radiotherapy, with or without concurrent chemotherapy, at Roswell Park Comprehensive Cancer Center (Buffalo, NY) between 2015 and 2017. Throughout a 7-week treatment course, patient mouth and throat soreness (MTS) was self-reported weekly using a validated oral mucositis questionnaire, with responses 0 (no) to 4 (extreme). Average treatment times from day 1 until the day before each mucositis survey were categorized into seven groups. Multivariable-adjusted marginal average scores (LSmeans) were estimated for the repeated- and maximum-MTS, using a linear-mixed model and generalized-linear model, respectively. RESULTS: Radiation treatment time was significantly associated with oral mucositis severity using both repeated-MTS (n = 1,156; P = 0.02) and maximum-MTS (n = 190; P = 0.04), with consistent patterns. The severity was lowest for patients treated during 8:30 to <9:30 am (LSmeans for maximum-MTS = 2.24; SE = 0.15), increased at later treatment times and peaked at early afternoon (11:30 am to <3:00 pm, LSmeans = 2.66-2.71; SEs = 0.16/0.17), and then decreased substantially after 3 pm. CONCLUSIONS: We report a significant association between radiation treatment time and oral mucositis severity in patients with head and neck cancer. IMPACT: Although additional studies are needed, these data suggest a potential simple treatment time solution to limit severity of oral mucositis during radiotherapy without increasing cost.

Thermogelling chitosan-based polymers for the treatment of oral mucosa ulcers.

Current treatments for oral mucosa-related ulcers use drugs to relieve pain and promote healing, but rarely consider drug resistance to bacterial infection in the microenvironment of the oral cavity or the prevention of bleeding from gingival mucosa ulcers. We herein report an injectable, thermogelling chitosan-based system to address these concerns. An aqueous solution of chitosan-based conjugates (chitosan-g-poly(N-isopropylacrylamide) [CS-g-PNIPAAM] including 1a [CS-g-PNIPAAM with less PNIPAAM] and 1b [CS-g-PNIPAAM with more PNIPAAM], and chitosan-g-poly(N-isopropylacrylamide)-g-polyacrylamide [CS-g-PNIPAAM-g-PAM] 3) could reversibly form semi-solid gels at physiological temperatures for easy application to oral cavity ulcer sites by injection. The chitosan-based conjugate thermogels prepared could inhibit both Gram-positive and Gram-negative bacteria and the two with higher chitosan and poly(N-isopropylacrylamide) contents (1a and 1b) promoted proliferation of gingival fibroblasts in vitro. These two thermogels also exhibited improved blood clotting in an in vivo rat study. Thermogels 1a and 1b effectively promoted ulcer healing and shortened ulcer healing times in an oral gingival mucosa ulcer model using Sprague Dawley (SD) rats. These thermogels showed no obvious toxicity to the main organs of SD rats undergoing gingival ulcer treatment. These results suggest that this antibacterial biomaterial could be a promising injectable therapeutic agent for the treatment for oral mucosa ulcers.

System, Method and Software for Calculation of a Cannabis Drug Efficiency Index for the Reduction of Inflammation.

There are many varieties of Cannabis sativa that differ from each other by composition of cannabinoids, terpenes and other molecules. The medicinal properties of these cultivars are often very different, with some being more efficient than others. This report describes the development of a method and software for the analysis of the efficiency of various cannabis extracts to detect the anti-inflammatory properties of the various cannabis extracts. The method uses high-throughput gene expression profiling data but can potentially use other omics data as well. According to the signaling pathway topology, the gene expression profiles are convoluted into the signaling pathway activities using a signaling pathway impact analysis (SPIA) method. The method was tested by inducing inflammation in human 3D epithelial tissues, including intestine, oral and skin, and then exposing these tissues to various extracts and then performing transcriptome analysis. The analysis showed a different efficiency of the various extracts in restoring the transcriptome changes to the pre-inflammation state, thus allowing to calculate a different cannabis drug efficiency index (CDEI).

Tart cherry (Prunus cerasus L.) fractions inhibit biofilm formation and adherence properties of oral pathogens and enhance oral epithelial barrier function.

Dental caries, candidiasis, and periodontal disease are the most common oral infections affecting a wide range of the population worldwide. The present study investigated the effects of two tart cherry (Prunus cerasus L.) fractions on important oral pathogens, including Candida albicans, Streptococcus mutans, and Fusobacterium nucleatum, as well as on the barrier function of oral epithelial cells. Procyanidins and quercetin and its derivatives were the most important constituents found in the tart cherry fractions. Although the fractions showed poor antimicrobial activity, they inhibited biofilm formation by the three oral pathogens in a dose-dependent manner. The tart cherry fractions also attenuated the adherence of C. albicans and S. mutans to a hydroxylapatite surface as well as the adherence of F. nucleatum to oral epithelial cells. Treating oral epithelial cells with the tart cherry fractions significantly enhanced the barrier function as determined by monitoring the transepithelial electrical resistance. In conclusion, this study showed that the tart cherry fractions and their bioactive constituents could be promising antiplaque compounds by targeting biofilm formation and adherence properties of oral pathogens. Furthermore, its property of increasing the epithelial barrier function may protect against microbial invasion of the underlying connective tissue.

Evaluation of the Effect of Topical Hypericum perforatum Oil on Excisional Palatal Wound Healing in Rabbits.

Aim: The aim of this study was to evaluate the effect of Hypericum perforatum (HP) oil on wound-healing process in rabbit palatal mucosa. Materials and Methods: Thirty-six New Zealand albino rabbits were randomly allocated to following groups; (1) HP oil (test, n = 18) and (2) olive oil (control, n = 18). Palatinal excisional wounds were created and the oils were topically applied (0.1 ml, 30 s, twice a day). Gingival biopsies were excised, and analyzed for re-epithelialization (RE) and granulation tissue maturation (GTM) on days 3, 7, and 14 after surgery. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were assessed using the immunohistochemical method. Apoptotic cells (ACs) were evaluated using TUNEL staining. Enzyme-linked immunosorbent assay was used to assess tissue catalase (CAT) and malondialdehyde (MDA) levels. Results: RE and GTM were completed earlier in the HP oil group than in the control group. The number of positively stained cells/vessels was higher in olive oil than in the test group on day 3 for FGF-2 and on days 3 and 7 for VEGF (p < 0.05). In contrast, on day 14, a higher number of vessels was observed in the HP oil group than in the control group. HP oil treatment reduced the number of ACs compared to olive oil (p < 0.05), but the difference during the healing period did not reach significance. Tissue CAT and MDA levels between groups were not different, and also the results were the same when the levels were analyzed by the evaluated time periods (p > 0.05). Conclusions: The results of this study demonstrated that topical HP oil treatment did not provide an additional benefit to its base, olive oil, in the early phase of secondary wound healing.

Mucoadhesive films based on gellan gum/pectin blends as potential platform for buccal drug delivery.

Films of gellan gum:pectin blends were prepared by solvent casting method. Gellan gum:pectin mass ratios were varied (4:1; 1:1; 1:4) at different concentrations (3% or 4%) and glycerol was used as plasticizer (1 or 2%). The films were thin (18-30 µm), translucent, flexible, and homogeneous. The surface pH was suitable for buccal application. All films reached high mechanical resistance and the mucoadhesive ability of them was evidenced. High ratio of gellan gum improved the mechanical resistance and the mucoadhesion of the films as well as the control of drug release rates. The films did not disintegrate in simulate saliva up to 24 h and curcumin release could be sustained up to 12 h. The set of data evidence that the films designed in this work represent a potential platform for buccal drug delivery.

An evaluation of the effects of caffeic acid phenethyl ester and Ankaferd blood stopper on secondary wound healing of oral mucosal tissue

Background/aim: Caffeic acid phenethyl ester (CAPE) and Ankaferd Blood Stopper (ABS) are considered to contribute to wound healing. The purpose of this study was to investigate the effect of ABS and CAPE on secondary wound healing of oral mucosal tissue. Materials and methods: In total, 63 male Sprague-Dawley rats were used in this study. The animals were randomly divided into three groups and anaesthetized with ketamine (8 mg/100 g, intraperitoneally): a control group, CAPE group, and ABS group. A full-thickness excisional wound was created using a 4 mm punch biopsy tool. Topical ABS and CAPE were then applied in each group for 7, 14, and 21 days (n = 7 in each group). The animals in each group were sacrificed after 7, 14, and 21 days. Palatal specimens were stained with haematoxylin-eosin. Vascular endothelial growth factor (VEGF) and tumour necrosis factor-inducible gene 6 (TSG-6) protein expressions were determined using the Western blot method. Results: Inflammation, vessel dilatation, and haemorrhages were significantly lower in the CAPE group as compared with these parameters in the other groups (P < 0.05). Fibrosis was significantly higher in the ABS group as compared with that in the other groups (P < 0.05). VEGF protein levels were elevated in the 21-day CAPE group and 7-day ABS group. The expression of TSG-6 increased in the 7-day CAPE group and 21-day ABS group. Conclusion: Based on our findings, ABS and CAPE had positive effects on the oral wound healing process.

Evaluation of the Impact of Oral Hygiene and Chamomile Tea in the Development of Oral Mucositis: Pilot Study / Avaliação do Impacto da Higiene Oral Associada ao Uso do Chá de Camomila no Desenvolvimento de Mucosite Oral: Estudo-Piloto / Evaluación del Impacto de la Higiene Oral y el Té de Manzanilla en el Desarrollo de la Mucositis Oral: Estudio Piloto

Introduction: The oral mucositis (OM) represents a frequent inflammatory condition in cancer patients, and poor oral hygiene has been related as a predisposing factor for its onset. Chamomile tea has been studied as an adjunctive therapy in the management of OM due to its analgesic and anti-inflammatory properties. Objective: The objective of this study was to evaluate the influence of chamomile tea associated with a rigorous oral hygiene in the OM prevention. Method: Randomized pilot clinical study, with 35 patients assigned to two groups. The case-group underwent oral hygiene control associated with the use of chamomile tea before starting the first cycle of chemotherapy, while the control group, there were no previous guidelines and prescriptions. Data about sociodemographic characteristics, the type of neoplasm and the chemotherapy scheme proposed were collected. The variables OM, salivary flow and pain associated to the oral cavity were evaluated, and statistical analysis was performed with significance level p <0.05. Results: It was observed that the majority of the patients had a mean age of 50 years, breast (57%) was the most prevalent tumor site and cyclophosphamide (52%), the most frequently used drug In this sample, no statistically significant result was observed in the two groups for OM, salivary flow and pain variables (p> 0.05). Conclusion: These data suggest that the use of chamomile tea and the accuracy of oral hygiene were not sufficient to prevent OM.

Introdução: A mucosite oral (MO) representa uma condição inflamatória frequente em pacientes oncológicos e uma higiene oral insatisfatória tem sido relacionada como fator predisponente para o seu surgimento. O chá de camomila vem sendo estudado como terapia adjuvante no manejo da MO em razão das suas propriedades analgésicas e anti-inflamatórias. Objetivo: Avaliar a influência do chá de camomila associada a uma rigorosa higiene oral na prevenção de MO. Método: Trata-se de um estudo-piloto clínico randomizado, no qual 35 pacientes foram alocados em dois grupos. O grupo-caso foi submetido ao controle de higiene oral associado ao uso do chá de camomila antes de iniciar o primeiro ciclo de quimioterapia; no grupo-controle, não houve orientações e prescrições prévias. Foram coletados dados referentes às características sociodemográficas, à neoplasia em questão e ao tipo de tratamento quimioterápico proposto. Foram avaliadas as variáveis MO, fluxo salivar e dor associada à cavidade oral, e realizada análise estatística com nível de significância p<0,05. Resultados: Observou-se que a maioria dos pacientes apresentava-se na quinta década de vida, a localização do tumor mais prevalente foi a mama (57%) e a droga mais utilizada por esses pacientes foi a ciclosfamida (52%). Nesta amostra, não foi observado resultado estatisticamente significativo entre os grupos, no que diz respeito às variáveis MO, fluxo salivar e dor (p>0,05). Conclusão: Os dados sugerem que o uso do chá de camomila e o rigor na higiene oral não foram suficientes para a prevenção da MO.

Introducción: La mucositis oral (MO) representa una afección inflamatoria frecuente en pacientes con cáncer, y la mala higiene bucal se ha relacionado como un factor predisponente para su aparición. El té de manzanilla se ha estudiado como una terapia adyuvante en el tratamiento de la OM debido a sus propiedades analgésicas y antiinflamatorias. Objetivo: El objetivo de este estudio fue evaluar la influencia del té de manzannilla asociado con una hygiene oral rigurosa en la prevención de la MO. Método: Fue un estudio clínico piloto aleatorizado, en el que treinta y cinco pacientes fueron asignados en dos grupos. El grupo de casos se sometió a un control de higiene oral asociado con el uso de té de manzanilla antes de comenzar el primer ciclo de quimioterapia, mientras que en el grupo de control, no había pautas ni recetas previas. Se recopilaron datos sobre las características sociodemográficas, el tipo de neoplasia y el esquema de quimioterapia propuesto. Se evaluaron las variables MO, flujo salival y dolor asociado a la cavidad oral, y se realizó un análisis estadístico con nivel de significancia p<0,05. Resultados: Se observó que la mayoría de los pacientes tenían una edad media de 50 años, el sitio del tumor más prevalente era la mama (57%) y el fármaco utilizado con mayor frecuencia era la ciclofamida (52%). En esta muestra, no se observaron resultados estadísticamente significativos entre los grupos con respecto a las variables MO, flujo salival y dolor (p>0,05). Conclusión: Estos datos sugieren que el uso de té de manzanilla y la precisión de la higiene oral no fueron suficientes para prevenir la MO.

Micronucleus Cytome Assays in Human Lymphocytes and Buccal Cells.

The micronucleus (MN) assay, applied in different surrogate tissues, is one of the best validated cytogenetic techniques for evaluating chromosomal damage in humans. The cytokinesis-block micronucleus cytome assay in peripheral blood lymphocytes (L-CBMNcyt) is the most frequently used method in biomonitoring human populations to evaluate DNA damage caused by exposure to genotoxic agents, micronutrient deficiency or excess and genetic instability. Furthermore, recent scientific evidence suggests an association between an increased MN frequency in lymphocytes and risk of cancer and other age-related degenerative diseases. The micronucleus cytome assay applied in buccal exfoliated cells (BMNCyt), provides a complementary method for measuring DNA damage and cytotoxic effects in an easily accessible tissue not requiring ex vivo/in vitro culture. The protocol for L-CBMNcyt described here, refers to the use of ex vivo whole blood method, involving 72 h of culture with the block of cytokinesis starting at 44 h. BMNCyt protocol reports the established method for sample collection, processing, slide preparation and scoring.

Novel Human Full-Thickness Three-Dimensional Nonkeratinized Mucous Membrane Model for Pharmacological Studies in Wound Healing.

INTRODUCTION: Efforts are increasingly aiming to develop in vitro models that can provide effective alternatives to in vivo experiments. The main aim of this study was the establishment of an in vitro model of the nonkeratinized mucous membrane that can be used as a standardized tool to evaluate biological and therapeutic effects of pharmaceuticals for mucosal wound healing. METHODS: We established a full-thickness in vitro model of the nonkeratinized mucous membrane. While histological examination was performed to assess morphological characteristics, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of treatment with a dexpanthenol-containing ointment after laser wounding. RESULTS: Performing histological and immunofluorescence analyses we proved that our model mimics the two distinctive layers of the mucous membrane - the stratified squamous epithelium and the lamina propria. We used this model to investigate molecular effects of a dexpanthenol-containing ointment that is commonly used for the wound treatment of mucous membranes. For that purpose, our model exhibits a unique feature in that dexpanthenol and proliferation-enhancing additives that may interfere with our studies are not required for the maintenance of the model culture. After setting standardized lesions with a nonsequential fractional ultrapulsed CO2 laser, topical treatment with the dexpanthenol-containing ointment enhanced wound closure in the model compared to placebo and untreated controls. Furthermore, microarray analysis revealed that the treatment of the laser-wounded model with the dexpanthenol-containing ointment evoked an upregulated expression of various genes related to accelerated wound healing. CONCLUSION: Overall, we verified that this novel mucous membrane model can be utilized in future to monitor ex vivo effects of various topical therapies on mucosa morphology, physiology, and gene expression. Our findings confirm the potential of the model as an in vitro tool for the replacement of pharmacological in vivo studies regarding mucosal wound healing.