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1.
PLoS One ; 18(10): e0291878, 2023.
Article in English | MEDLINE | ID: mdl-37851692

ABSTRACT

This study aimed to investigate the relationship between food choices and periodontal health status (PHS) in adults who receive care through a public health system. We evaluated food preferences and periodontal status in a sample of 442 individuals with at least eight natural teeth. We employed the Food Frequency Questionnaire (FFQ) to assess food choices and the Periodontal Screening and Recording (PSR) instrument to evaluate periodontal health status during clinical appointments. Fisher's discriminant analysis was used to differentiate the participants according to PHS severity within three age-ranges (18-39; 40-59 and > 60 years-old). The results showed that the prevalence of overweight/obesity was high in all age groups (above 65%), and BMI increased with age, accompanied by an increase in the prevalence of chronic diseases. A lower preference for natural foods and a higher intake of processed and ultra-processed foods, along with a high waist circumference and diabetes, were associated with a poorer periodontal health status. In the 18-39 age group, a lower waist circumference was associated with healthier periodontal status. In the 40-59 age group, a worse periodontal status resulted from a higher frequency of diabetes, lower intake of green leafy vegetables, olive oil, and fruit, and higher intake of industrialized juice. Conversely, a healthier periodontal status was associated with a lower frequency of diabetes and higher intake of fruit and vegetables. In the > 60age group, the worst periodontal status was associated with male sex. Overall, the study highlights the possible beneficial role of a healthy diet in maintaining periodontal health, particularly for those who receive care through a public health system.


Subject(s)
Diabetes Mellitus , Food Preferences , Humans , Male , Adult , Middle Aged , Diet , Energy Intake , Body Mass Index , Feeding Behavior , Vegetables , Fruit
2.
ACS Omega ; 8(19): 16713-16721, 2023 May 16.
Article in English | MEDLINE | ID: mdl-37214671

ABSTRACT

Filamentous fungi are an essential source of bioactive mycotoxins. Recent efforts have focused on developing antifungal agents that are effective against invasive yeasts, such as Candida spp. By screening fungal strains isolated from regions surrounding the Chernobyl nuclear power plant disaster for antifungal activity against Candida albicans, we found that Aspergillus melleus IMV 01140 produced compounds that inhibited the growth of the yeast. The active compound produced by A. melleus was isolated and found to be neoaspergillic acid, a compound that is closely related to aspergillic acid. While aspergillic acid and its derivatives have been characterized and were found to have antibacterial and antifungal properties, neoaspergillic acid has been much less studied. Even though neoaspergillic acid and related compounds were found to have antibacterial and antitumoral effects, further investigation into this group of compounds is limited by challenges associated with large-scale production, isolation, and purification. The production of neoaspergillic acid has been shown to require co-cultivation methods or special growth conditions. In this work, neoaspergillic acid and related compounds were found to be produced by A. melleus under laboratory growth conditions. The biosynthetic gene cluster of neoaspergillic acid was predicted using the aspergillic acid gene cluster as a model. The biosynthetic pathway for neoaspergillic acid was then confirmed by establishing an in vitro CRISPR-ribonucleoprotein system to individually delete genes within the cluster. A negative transcriptional factor, mcrA, was also eliminated to further improve the production of neoaspergillic acid and the related compounds for future studies.

3.
J Periodontol ; 94(3): 364-375, 2023 03.
Article in English | MEDLINE | ID: mdl-36321899

ABSTRACT

BACKGROUND: Population studies consistently demonstrate a greater prevalence of chronic diseases, including oral diseases, among underrepresented minorities. This retrospective study aimed to measure and describe the prevalence and extent of periodontitis among adults seeking dental care within an academic practice-based network in rural North Carolina. METHODS: This study used de-identified electronic health record (EHR) data from 2011 to 2017 of adult dentate patients (aged ≥30 years) seeking dental care who received a comprehensive periodontal examination at one of nine networked clinical centers. Periodontitis prevalence was calculated using CDC/AAP case definitions, along with extent (%) scores for periodontal parameters. Comparisons focused on age, sex, race, ethnicity, tobacco use, diabetes status, payer or insurance status, plaque scores, and the number of teeth. RESULTS: EHR data for 10,544 adult patients (60.5% female) indicated 79.8% had some form of periodontitis. This patient population was diverse: 22.6% Black, 4.4% American Indian, and 53.8% White, with 4.8% self-identified as Hispanic. Patients 50 years and older showed greater mean extent scores for clinical attachment levels relative to patients 30 to 49 years. Males exhibited greater periodontitis than females (p = 0.001). Blacks showed significantly (p < 0.001) greater periodontitis prevalence relative to Whites. Hispanics also showed a greater prevalence of periodontitis (p < 0.001) relative to non-Hispanics. Significantly greater periodontitis was also noted for tobacco users (p < 0.001) but not for diabetes or payer status. A multiple logistic regression analysis of periodontitis prevalence confirmed significant associations for periodontitis for age, sex, race, ethnicity, tobacco use, high plaque scores, and the number of teeth (p < 0.001), but not diabetes or payer status. CONCLUSIONS: The data document that racial and ethnic inequalities in periodontal health occur within the population of adults residing in rural communities in North Carolina and seeking dental care.


Subject(s)
Diabetes Mellitus , Periodontitis , Male , Adult , Humans , Female , North Carolina/epidemiology , Retrospective Studies , Rural Population , Periodontitis/epidemiology , Dental Care , Prevalence
4.
Diabetol Metab Syndr ; 14(1): 80, 2022 Jun 08.
Article in English | MEDLINE | ID: mdl-35676689

ABSTRACT

BACKGROUND: Candlenut (CN) has been used indiscriminately for weight loss. In vivo effects of CN in different doses are scarce. OBJECTIVE: To evaluate the effects of CN ingestion in obese rats. DESIGN: Thirty animals (obese and non-obese) received one of three different types of treatments: placebo, CN ingestion in a popular therapeutic regimen (8 days with oral administration of 0.2 mg/kg followed by 20 days with doses of 0.4 mg/kg), and ingestion of a doubled popular dose-called 2CN. Treatment was maintained for 28 days. RESULTS: The fatty acid profile of CN indicated mainly linolelaidic and palmitoleic acids. Rats receiving CN and 2CN showed reduced plasmatic levels of glucose and lipoproteins (p < 0.05). A dose-dependent carcass fat reduction was observed (p < 0.05). Blood levels of aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) reduced with CN and increased with 2CN doses (p < 0.05). Alanine aminotransferase (ALT) and the atherogenic index remained similar among all treatments (p > 0.05). Hepatic vacuolation decreased with CN, but the 2CN dose produced mononuclear leucocyte infiltrate. CONCLUSIONS: Although CN presented beneficial effects on the metabolism of rats, it also caused increased risk of liver damage.

5.
Front Oral Health ; 3: 835902, 2022.
Article in English | MEDLINE | ID: mdl-35187533

ABSTRACT

Aggregatibacter actinomycetemcomitans (Aa) is abundant within the microbial dysbiotic community of some patients with periodontitis. Aa outer membrane protein 29 (OMP29), a member of the OMPA family, mediates the invasion of Aa to gingival epithelial cells (GECs). This study evaluated the effect of OMP29 and its paralogue OMP29par on the response of GECs to Aa. The omp29 or/and omp29 par deletion mutants AaΔ29, AaΔ29P, and AaΔ29Δ29P were constructed, and recombinant Aa OMP29His was obtained. Microarray analysis and the evaluation of cxcl-8 gene expression were performed to examine the response of GECs line OBA-09 to Aa and its mutants. The expression of cxcl-8 and its product CXCL-8 was examined in LPS-stimulated OBA-09 cells with Aa OMP29His. Proteomics analysis showed that the deletion of omp29 led to overexpression of both OMP29par and another membrane protein OMP39, the expression of which was further increased in AaΔ29Δ29P. OBA-09 cells challenged with AaΔ29Δ29P exhibited a higher expression of cxcl-8 in comparison to wildtype Aa strain AaD7S or single-deletion mutants AaΔ29 or AaΔ29P. LPS-stimulated OBA-09 cells challenged with Aa OMP29His showed reduced expressions of cxcl-8 and its product CXCL-8. OBA-09 cells challenged with AaΔ29Δ29P in comparison to Aa strain AaD7S resulted in higher expressions of genes involved in apoptosis and inflammatory response such as bcl2, birc3, casp3, c3, ep300, fas, fosb, grb2, il-1α, il-1ß, il-6, cxcl-8, nr3c1, prkcq, socs3, and tnfrsf1ß and reduced expressions of cd74, crp, faslg, tlr1, and vcam1. The results suggested a novel strategy of Aa, mediated by OMP29 and OMP29par, to evade host immune response by inhibiting CXCL-8 expression and modulating the genes involved in apoptosis and inflammatory response in GECs. Pending further confirmation, the strategy might interfere with the recruitment of neutrophils and dampen the host inflammatory response, leading to a more permissive subgingival niche for bacterial growth.

6.
Nat Prod Res ; 36(6): 1621-1625, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33729064

ABSTRACT

We reported the in vitro anti-HIV-1 activity, cytotoxicity, cytokines expression and chemical profile of Anadenanthera colubrina. Cytotoxicity was evaluated on TZM-bl, HL2/3 cells and macrophages. Anti-HIV-1 activity was determined by Luciferase assay (TZM-bl cells) and by HIV-p24 quantification (macrophages) assessed by ELISA. TZM-bl and HL2/3 cells were used to determine cell-cell fusion inhibition. Cytokines expression was assessed by ELISA. Chemical composition was determined by Gas Chromatography Coupled to Mass Spectrometry. At 66.6 µg/mL, the extract maintained the cell viability above 90%. At 33.28 µg/mL, the extract reduced 82.8% of HIV-1 infection (TZM-bl cells) and HIV-p24 expression (macrophages). The extract inhibited approximately 70% of TZM-bl and HL2/3 cells fusion. Extract did't induce inflammatory response. Phytochemical analysis showed presence of flavonoid, phenolic acids, fatty acids and sugars. This is the first study presenting the anti-HIV effect of A. colubrina, showing low cytotoxicity and no inflammatory stimuli, important requirements for a microbicide development.


Subject(s)
Colubrina , HIV Infections , HIV-1 , Gas Chromatography-Mass Spectrometry , Humans , Plant Extracts/pharmacology
7.
Front Pharmacol ; 12: 629778, 2021.
Article in English | MEDLINE | ID: mdl-34168555

ABSTRACT

Oral candidiasis is one of the most common fungal infections in humans. Its incidence has increased widely, as well as the antifungal resistance, demanding for the search for novel antifungal therapeutic agents. Anadenanthera colubrina (Vell.) Brenan is a plant species that has been proven to possess pharmacological effects, including antifungal and anti-inflammatory activities. This study evaluated in vitro the effects of standardized A. colubrina extract on virulence factors of Candida albicans and its regulation on immune response through C. albicans-host interaction. Antifungal activity was evaluated by Broth Microdilution Method against reference Candida strains (C. albicans, C. glabrata, C. tropicalis; C. dubliniensis). Anti-biofilm effect was performed on C. albicans mature biofilm and quantified by CFU/mL/g of biofilm dry weight. Proleotlytic enzymatic activities of proteinase and phospholipase were assessed by Azocasein and Phosphatidylcholine assays, respectively. Cytotoxicity effect was determined by Cell Titer Blue Viability Assay on Human Gingival Fibroblasts. Co-cultured model was used to analyze C. albicans coexisting with HGF by Scanning Electron Microscopy and fluorescence microscopies; gene expression was assessed by RT-PCR of C. albicans enzymes (SAP-1, PLB-1) and of host inflammatory cytokines (IL-6, IL-8, IL-1ß, IL-10). Cytokines secretion was analysed by Luminex. The extract presented antifungal effect with MIC<15.62 µg/ml against Candida strains. Biofilm and proteolytic activity were significant reduced at 312.4 µg/ml (20 × 15.62 µg/ml) extract concentration. Cell viability was maintained higher than 70% in concentrations up to 250 µg/ml (LD50 = 423.3 µg/ml). Co-culture microscopies demonstrated a substantial decreased in C. albicans growth and minimal toxicity against host cells. Gene expressions of SAP-1/PLB-1 were significantly down-regulated and host immune response was modulated by a significant decreased on IL-6 and IL-8 cytokines secretion. A. colubrina had antifungal activity on Candida strains, antibiofilm, and anti-proteolytic enzyme effects against C. albicans. Presented low cytotoxicity to the host cells and modulatory effects on the host immune response.

9.
Braz Oral Res ; 35: e046, 2021.
Article in English | MEDLINE | ID: mdl-33729296

ABSTRACT

Several guidelines for dental practice have been published by dental associations and regulatory boards since the beginning of the pandemic. Initially, all non-emergency dental treatment were suspended. Healthcare personnel around the world are gradually expanding back to elective procedures. International updated recommendations alert that professionals must maintain regular observation of local health department reports, ensure personal protective equipment, and screen all patients for COVID-19 signs and symptoms. Telehealth strategies, patient screening, rescheduling when presenting COVID-19 symptoms and/or history of contact with infected people and hand/environment hygiene practices are reinforced. Appropriate cleaning and surface disinfection are mandatory. The dental staff must be trained to use appropriate Personal Protective Equipment (PPE), following a risk assessment and standard precautions: gloves; fluid resistant disposable gown, eye protection (face shield or goggles) and a medical mask. A fit tested N95 or KN95 respirator (or higher) is recommended when aerosol generating procedures are performed. Only essential accompanying persons should attend to dental appointment with the patient and must wear a cloth face covering or facemask. Social distancing and mask wearing by all staff are necessary in all areas of the office. Dental health care providers should keep up to date to the current guidance of clinical practice during the pandemic.


Subject(s)
COVID-19 , Pandemics , Dental Care , Humans , Infection Control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics/prevention & control , SARS-CoV-2
10.
Nat Prod Res ; 35(6): 1064-1069, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31429300

ABSTRACT

The emphasis of the present study is to evaluate a natural product and the potential microbicide activity using a dual chamber infection method. Malva sylvestris extracts and fractions were screened for anti-HIV activity by measuring the virus-antibody neutralization. Plant extracts with strong antiviral activity working in nanomolar or picomolar range can be used to enhance the activity of synthetic compounds and work as anti-HIV agents. The aqueous fraction (AF) of M. sylvestris demonstrated antiviral activity in a model with epithelial and blood cell lines. The AF showed an effective antiviral potential on the TZM-bl cells with reduction scores higher than 60% of infectivity. Quantification of p24 in the supernatant of the co-culture model demonstrated a reduction in the number of viral particles after AF treatment (p < 0.05). Cytokines were quantified and all signaling inflammatory markers; IL1-alpha, IL-beta, IL-6, IL-8 and GM-CSF (p < 0.05) were modulated by positive control and AF treatments. In particular, IL-6 had lower levels of expression in Malva groups when compared to the Zidovudine positive control group. Natural occurring derivatives of M. sylvestris demonstrated to work inhibiting reverse transcriptase enzyme action. M. sylvestris contains highly potential anti-HIV-1 BaL components and may be considered a potential source for new formulations in the development of topical microbicides.


Subject(s)
HIV Infections/drug therapy , HIV-1/drug effects , Malva/chemistry , Animals , Anti-HIV Agents/pharmacology , Cell Death/drug effects , Cell Line , Cell Survival/drug effects , Chemical Fractionation , Cytokines/metabolism , HIV Core Protein p24/metabolism , Humans , Mice , Plant Extracts/pharmacology
11.
Braz Oral Res ; 34: e041, 2020 May 08.
Article in English | MEDLINE | ID: mdl-32401931

ABSTRACT

The expansion of coronavirus disease 2019 (COVID-19) throughout the world has alarmed all health professionals. Especially in dentistry, there is a growing concern due to it's high virulence and routes of transmission through saliva aerosols. The virus keeps viable on air for at least 3 hours and on plastic and stainless-steel surfaces up to 72 hours. In this sense, dental offices, both in the public and private sectors, are high-risk settings of cross infection among patients, dentists and health professionals in the clinical environment (including hospital's intensive dental care facilities). This manuscript aims to compile current available evidence on prevention strategies for dental professionals. Besides, we briefly describe promising treatment strategies recognized until this moment. The purpose is to clarify dental practitioners about the virus history and microbiology, besides guiding on how to proceed during emergency consultations based on international documents. Dentists should consider that a substantial number of individuals (including children) who do not show any signs and symptoms of COVID-19 may be infected and can disseminate the virus. Currently, there is no effective treatment and fast diagnosis is still a challenge. All elective dental treatments and non-essential procedures should be postponed, keeping only urgent and emergency visits to the dental office. The use of teledentistry (phone calls, text messages) is a very promising tool to keep contact with the patient without being at risk of infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Dental Care/standards , Oral Health/standards , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Practice Patterns, Dentists'/standards , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/transmission , Dentists/standards , Humans , Pneumonia, Viral/transmission , Practice Guidelines as Topic , Risk Factors , SARS-CoV-2
12.
Preprint in English | SciELO Preprints | ID: pps-270

ABSTRACT

The expansion of coronavirus disease 2019 (COVID-19) throughout the world has alarmed all health professionals. Especially in dentistry, there is a growing concern due to it's high virulence and routes of transmission through saliva aerosols. The virus keeps viable on air for at least 3 hours and on plastic and stainless-steel surfaces up to 72 hours. In this sense, dental offices, both in the public and private sectors, are high-risk settings of cross infection among patients, dentists and health professionals in the clinical environment (including hospital's intensive dental care facilities). This manuscript aims to compile current available evidence on prevention strategies for dental professionals. Besides, we briefly describe promising treatment strategies recognized until this moment. The purpose is to clarify dental practitioners about the virus history and microbiology, besides guiding on how to proceed during emergency consultations based on international documents. Dentists should consider that a substantial number of individuals (including children) who do not show any signs and symptoms of COVID-19 may be infected and can disseminate the virus. Currently, there is no effective treatment and fast diagnosis is still a challenge. All elective dental treatments and non-essential procedures should be postponed, keeping only urgent and emergency visits to the dental office. The use of teledentistry (phone calls, text messages) is a very promising tool to keep contact with the patient without being at risk of infection.

13.
Braz. oral res. (Online) ; 34: e041, 2020. graf
Article in English | LILACS, BBO - Dentistry | ID: biblio-1132709

ABSTRACT

Abstract The expansion of coronavirus disease 2019 (COVID-19) throughout the world has alarmed all health professionals. Especially in dentistry, there is a growing concern due to it's high virulence and routes of transmission through saliva aerosols. The virus keeps viable on air for at least 3 hours and on plastic and stainless-steel surfaces up to 72 hours. In this sense, dental offices, both in the public and private sectors, are high-risk settings of cross infection among patients, dentists and health professionals in the clinical environment (including hospital's intensive dental care facilities). This manuscript aims to compile current available evidence on prevention strategies for dental professionals. Besides, we briefly describe promising treatment strategies recognized until this moment. The purpose is to clarify dental practitioners about the virus history and microbiology, besides guiding on how to proceed during emergency consultations based on international documents. Dentists should consider that a substantial number of individuals (including children) who do not show any signs and symptoms of COVID-19 may be infected and can disseminate the virus. Currently, there is no effective treatment and fast diagnosis is still a challenge. All elective dental treatments and non-essential procedures should be postponed, keeping only urgent and emergency visits to the dental office. The use of teledentistry (phone calls, text messages) is a very promising tool to keep contact with the patient without being at risk of infection.


Subject(s)
Humans , Pneumonia, Viral/prevention & control , Oral Health/standards , Dental Care/standards , Coronavirus Infections/prevention & control , Practice Patterns, Dentists'/standards , Pandemics/prevention & control , Betacoronavirus/pathogenicity , Pneumonia, Viral/transmission , Risk Factors , Practice Guidelines as Topic , Coronavirus Infections/transmission , Dentists/standards , SARS-CoV-2 , COVID-19
14.
Front Microbiol ; 9: 2638, 2018.
Article in English | MEDLINE | ID: mdl-30467497

ABSTRACT

The aim of this in vitro study was to evaluate the effects of monolaurin against Aggregatibacter actinomycetemcomitans (Aa) and determine their effects on the host transcriptome and metabolome, using an oral cell/bacteria co-culture dual-chamber model to mimic the human periodontium. For this, the Aa, was applied to cross the monolayer of epithelial keratinocytes (OBA-9) to reach the fibroblasts layer (HGF-1) in the basal chamber. The Monolaurin treatments (25 or 50 µM) were added immediately after the inoculation of the dual-chamber with Aa. After 24 h, the transcriptional factors and metabolites produced were quantified in the remaining cell layers (insert and basal chamber) and in supernatant released from the cells. The genes IL-1α, IL-6, IL-18, and TNF analyzed in HGF-1 concentrations showed a decreased expression when treated with both concentration of Monolaurin. In keratinocytes, the genes IL-6, IL-18, and TNF presented a higher expression and the expression of IL-1α decreased when treated with the two cited concentrations. The production of glycerol and pyruvic acid increased, and the 2-deoxytetronic acid NIST, 4-aminobutyric acid, pinitol and glyceric acid, presented lower concentrations because of the treatment with 25 and/or 50 µM of Monolaurin. Use of monolaurin modulated the immune response and metabolite production when administered for 24 h in a dual-chamber model inoculated with A. actinomycetemcomitans. In summary, this study indicates that monolaurin had antimicrobial activity and modulated the host immune response and metabolite production when administered for 24 h in a dual-chamber model inoculated with A. actinomycetemcomitans.

15.
Int J Dent ; 2018: 2393146, 2018.
Article in English | MEDLINE | ID: mdl-30186325

ABSTRACT

Current treatments for Candida albicans infection are limited due to the limited number of antifungal drugs available and the increase in antifungal resistance. Curcumin is used as a spice, food preservative, flavoring, and coloring agent that has been shown to have many pharmacological activities. Thus, this study evaluated the modulatory effects of curcumin on major virulence factors associated with the pathogenicity of C. albicans. The minimum inhibitory concentration (MIC) of curcumin against C. albicans (SC5314) was determined. Biofilm formation was quantified and the proteinase and phospholipase secretion was measured. The cytotoxicity was tested in oral fibroblast cells. A cocultured model was used to analyze the gene expression of proinflammatory cytokines (IL-1ß, IL-1α, and IL-6) from host cells, as well SAP-1 and PLB-1 by RT-PCR. The MIC was between 6.25 and 12.5 µM, and the activity of proteinase enzyme was significantly decreased in biofilms treated with curcumin. However, proteinase gene expression was not downregulated after curcumin treatment. Furthermore, gene expressions of host inflammatory response, IL-1ß and IL-1α, were significantly downregulated after exposure to curcumin. In conclusion, curcumin exhibited antifungal activity against C. albicans and modulated the proteolytic enzyme activities without downregulating the gene expression. In host inflammatory response, curcumin downregulated IL-1ß and IL-1α gene expression.

16.
Biol Pharm Bull ; 41(8): 1299-1302, 2018.
Article in English | MEDLINE | ID: mdl-30068882

ABSTRACT

Monolaurin is a natural compound that has been known for its broad antimicrobial activities. We evaluate the antifungal activity of monolaurin against Candida albicans biofilms in vivo using a novel bioluminescent model to longitudinally monitor oral fungal infection. Oral fungal infection in vivo was performed using bioluminescent engineered C. albicans (SKCa23-ActgLUC) biofilms on Balb/c mice. The antifungal activity of monolaurin was determined by comparing three groups of mice (n=5/group): monolaurin, vehicle control, and positive control (nystatin). All mice were immunosuppressed with cortisone acetate and oral topical treatments were applied for 5 d. In vivo imaging system (IVIS) imaging was used to monitor the progression of infection over a 5-d period. Total photon flux and ex vivo microbiological analysis of the excised tongues were used to determine the overall fungal burden. Oral topical treatments of monolaurin have resulted in a significant decrease (p<0.05) in the total photon flux over 4 and 5 d post-infection in comparison to the vehicle control group. Furthermore, monolaurin treated group had a significant decrease in colony formation unit of tongue tissue compared to the vehicle control. Our findings support monolaurin as a promising antifungal compound in vivo, which may translate to its future use in the treatment of oral candidiasis.


Subject(s)
Antifungal Agents/therapeutic use , Candidiasis, Oral/drug therapy , Laurates/therapeutic use , Monoglycerides/therapeutic use , Animals , Biofilms/drug effects , Candida albicans/drug effects , Candida albicans/physiology , Candidiasis, Oral/microbiology , Mice, Inbred BALB C , Tongue/microbiology
17.
Phytother Res ; 32(4): 750-754, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29377427

ABSTRACT

Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red propolis, a unique Apis melifera type of propolis botanically originated from Dalbergia ecastophyllum. Although these molecules have relevant biological effects, including anticancer and immunomodulatory activities, their mechanism(s) of action and the affected pathways remain largely unknown. Here, we carried out a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol on the whole-genome expression in human tumor cells, particularly cancer-related target proteins. HeLa cells were exposed to the compounds at IC20 and genomic information of treated cells was analyzed using the Illumina transcriptome system and GeneGo MetaCore software. Our results showed that vestitol (IC20  = 214.7 µM) reduced the expression of genes enrolled with the alpha tubulin (fold -3.7), tubulin in microtubules (fold -3.7), and histone h3 (fold = -3.03), and that treatment with neovestitol (IC20  = 102.91 µM) downregulated prostaglandin E synthase gene (fold = -3.12), which are considered ideal targets for anticancer therapy. These data open avenues for the study of vestitol and neovestitol as potential promising candidates for anticancer therapy. Toxicological, non-clinical, and clinical validation of the findings presented herein is needed.


Subject(s)
Flavonoids/metabolism , Isoflavones/metabolism , Pharmacogenomic Testing/methods , Propolis/pharmacology , Animals , Bees , Brazil , Down-Regulation , HeLa Cells , Humans
18.
BMC Microbiol ; 17(1): 53, 2017 03 07.
Article in English | MEDLINE | ID: mdl-28270109

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the effects of ß-glucan on the expression of inflammatory mediators and metabolomic profile of oral cells [keratinocytes (OBA-9) and fibroblasts (HGF-1) in a dual-chamber model] infected by Aggregatibacter actinomycetemcomitans. The periodontopathogen was applied and allowed to cross the top layer of cells (OBA-9) to reach the bottom layer of cells (HGF-1) and induce the synthesis of immune factors and cytokines in the host cells. ß-glucan (10 µg/mL or 20 µg/mL) were added, and the transcriptional factors and metabolites produced were quantified in the remaining cell layers and supernatant. RESULTS: The relative expression of interleukin (IL)-1-α and IL-18 genes in HGF-1 decreased with 10 µg/mL or 20 µg/mL of ß-glucan, where as the expression of PTGS-2 decreased only with 10 µg/mL. The expression of IL-1-α increased with 20 µg/mL and that of IL-18 increased with 10 µg/mL in OBA-9; the expression of BCL 2, EP 300, and PTGS-2 decreased with the higher dose of ß-glucan. The production of the metabolite 4-aminobutyric acid presented lower concentrations under 20 µg/mL, whereas the concentrations of 2-deoxytetronic acid NIST and oxalic acid decreased at both concentrations used. Acetophenone, benzoic acid, and pinitol presented reduced concentrations only when treated with 10 µg/mL of ß-glucan. CONCLUSIONS: Treatment with ß-glucans positively modulated the immune response and production of metabolites.


Subject(s)
Aggregatibacter actinomycetemcomitans/drug effects , Aggregatibacter actinomycetemcomitans/physiology , Cytokines/drug effects , Gene Expression/drug effects , Host-Pathogen Interactions , Metabolome/drug effects , beta-Glucans/pharmacology , Acetophenones/metabolism , Anti-Infective Agents/pharmacology , Benzoic Acid/metabolism , Cell Culture Techniques/methods , Cell Line , Coculture Techniques , Cyclooxygenase 2/metabolism , Cytokines/genetics , Cytokines/immunology , E1A-Associated p300 Protein/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Host-Pathogen Interactions/immunology , Humans , Hydroxybutyrates/metabolism , Immunomodulation , Inositol/analogs & derivatives , Inositol/metabolism , Interleukin-18/genetics , Interleukin-1alpha/genetics , Keratinocytes/drug effects , Keratinocytes/metabolism , Lymphoma, B-Cell/metabolism , Metabolome/genetics , Metabolome/immunology , Mouth/immunology , Mouth/microbiology , Oxalic Acid/metabolism , Periodontal Diseases/immunology , Periodontal Diseases/microbiology , Proto-Oncogene Proteins c-bcl-2/metabolism , Real-Time Polymerase Chain Reaction , beta-Glucans/administration & dosage , beta-Glucans/metabolism , gamma-Aminobutyric Acid/metabolism
19.
Arch Oral Biol ; 76: 76-83, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27659902

ABSTRACT

Flavonoids are a subdivision of polyphenols, a versatile class of natural compounds that represent secondary metabolites from higher plants and are abundant in human diet. Various protective effects of flavonoids have been reported, including antimicrobial and antifungal activities. Due to the nature of oral candidiasis and the increased use of antifungal agents, several drug-resistant strains have emerged making it impractical to rely on one standard therapeutic regime. The aim of this review is to summarize the antifungal activity of some examples of the major subclasses of flavonoids in pure extract forms against C. albicans in vitro, as reported in literature over the past 10 years (2004-2015). In addition, this review outlines the potential mechanism of actions of flavonoids studied in vitro, which may contribute to a better understanding of flavonoids as multi-targets agents in the treatment and/or prevention of oral candidiasis in clinical settings.


Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Flavonoids/pharmacology , Apoptosis/drug effects , Candidiasis, Oral/drug therapy , Cell Wall/drug effects , Drug Resistance, Fungal , In Vitro Techniques , Microbial Sensitivity Tests
20.
PLoS One ; 11(6): e0157188, 2016.
Article in English | MEDLINE | ID: mdl-27284694

ABSTRACT

Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 µM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use.


Subject(s)
Antifungal Agents/therapeutic use , Biofilms/drug effects , Candida albicans/drug effects , Candidiasis, Oral/drug therapy , Chalcones/therapeutic use , Mouth/microbiology , Animals , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Candida albicans/physiology , Candidiasis, Oral/microbiology , Candidiasis, Oral/pathology , Cell Line , Chalcones/chemistry , Chalcones/pharmacology , Coculture Techniques , Fibroblasts/drug effects , Fibroblasts/microbiology , Fibroblasts/pathology , Glycyrrhiza/chemistry , Humans , Interleukins/analysis , Mice , Mouth/pathology
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