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COVID-19, caused by the SARS-COV-2 virus, induces numerous immunological reactions linked to the severity of the clinical condition of those infected. The surface Spike protein (S protein) present in Sars-CoV-2 is responsible for the infection of host cells. This protein presents a high rate of mutations, which can increase virus transmissibility, infectivity, and immune evasion. Therefore, we propose to evaluate, using immunoinformatic techniques, the predicted epitopes for the S protein of seven variants of Sars-CoV-2. MHC class I and II epitopes were predicted and further assessed for their immunogenicity, interferon-gamma (IFN-γ) inducing capacity, and antigenicity. For B cells, linear and structural epitopes were predicted. For class I MHC epitopes, 40 epitopes were found for the clades of Wuhan, Clade 2, Clade 3, and 20AEU.1, Gamma, and Delta, in addition to 38 epitopes for Alpha and 44 for Omicron. For MHC II, there were differentially predicted epitopes for all variants and eight equally predicted epitopes. These were evaluated for differences in the MHC II alleles to which they would bind. Regarding B cell epitopes, 16 were found in the Wuhan variant, 14 in 22AEU.1 and in Clade 3, 15 in Clade 2, 11 in Alpha and Delta, 13 in Gamma, and 9 in Omicron. When compared, there was a reduction in the number of predicted epitopes concerning the Spike protein, mainly in the Delta and Omicron variants. These findings corroborate the need for updates seen today in bivalent mRNA vaccines against COVID-19 to promote a targeted immune response to the main circulating variant, Omicron, leading to more robust protection against this virus and avoiding cases of reinfection. When analyzing the specific epitopes for the RBD region of the spike protein, the Omicron variant did not present a B lymphocyte epitope from position 390, whereas the epitope at position 493 for MHC was predicted only for the Alpha, Gamma, and Omicron variants.
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Numerous commercial tests for the serological diagnosis of COVID-19 have been produced in recent years. However, it is important to note that these tests exhibit significant variability in their sensitivity, specificity, and accuracy of results. Therefore, the objective of this study was to utilize bioinformatics tools to map SARS-CoV-2 peptides, with the goal of developing a new serological diagnostic test for COVID-19. Two peptides from the S protein and one from the N protein were selected and characterized in silico, chemically synthesized, and used as a serological diagnostic tool to detect IgM, IgG, and IgA anti-SARS-CoV-2 antibodies through the ELISA technique, confirmed as positive and negative samples by RT-qPCR or serology by ELISA. The results showed a sensitivity, specificity, Positive Predictive Value and Negative Predictive Value of 100% (p < 00001, 95% CI) for the proposed test. Although preliminary, this study brings proof-of-concept results that are consistent with the high-performance rates of the ELISA test when compared to other well-established methods for diagnosing COVID-19.
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The pathogenic nature of infections caused by Candida spp. underscores the necessity for novel therapeutic agents. Extracts of Schinopsis brasilienses Engl are \ a promising source of agents with antifungal effects. This study aimed to assess the antifungal potential of the leaf extract of S. brasilienses. The antifungal activity was evaluated by determining the minimum inhibitory concentrations and fungicide concentrations (MIC and MFC). The antibiofilm potential was assessed by counting colony-forming units/mL. The study examined the inhibition kinetics of fungal growth and potential synergism between gallic acid or the extract and nystatin using the Checkerboard method. Cytotoxicity was evaluated through the MTT assay. The extract exhibited antifungal effect against all tested strains, with MIC and MFC ranging from 31.25-250 µg/mL. Gallic acid, the main isolated compound, displayed a MIC of 2000 µg/mL. The extract of S. brasilienses at 31.25 µg/mL inhibited the formation of biofilm by C. albicans and significantly reduced the mass of mature biofilm after 24 and 48 h (p < 0. 05). At a concentration of 125 µg/mL, the extract demonstrated significant inhibition of fungal growth after 6 hours. The combination of gallic acid or extract with nystatin did not exhibit synergistic or antagonistic effect. Furthermore, the extract did not induce cytotoxicity to a human cell line. The extract of S. brasiliensis demonstrates antifungal activity against Candida, generally exhibiting fungicidal action and capacity to inhibit biofilm formation as well as reduce mature biofilms. Additionally, the extract showed low cytotoxicity to human cells.
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Anacardiaceae , Candida , Humanos , Antifúngicos , Nistatina , Candida albicans , Biopelículas , Ácido Gálico , Extractos VegetalesRESUMEN
Abstract The pathogenic nature of infections caused by Candida spp. underscores the necessity for novel therapeutic agents. Extracts of Schinopsis brasilienses Engl are / a promising source of agents with antifungal effects. This study aimed to assess the antifungal potential of the leaf extract of S. brasilienses. The antifungal activity was evaluated by determining the minimum inhibitory concentrations and fungicide concentrations (MIC and MFC). The antibiofilm potential was assessed by counting colony-forming units/mL. The study examined the inhibition kinetics of fungal growth and potential synergism between gallic acid or the extract and nystatin using the Checkerboard method. Cytotoxicity was evaluated through the MTT assay. The extract exhibited antifungal effect against all tested strains, with MIC and MFC ranging from 31.25-250 μg/mL. Gallic acid, the main isolated compound, displayed a MIC of 2000 μg/mL. The extract of S. brasilienses at 31.25 μg/mL inhibited the formation of biofilm by C. albicans and significantly reduced the mass of mature biofilm after 24 and 48 h (p < 0. 05). At a concentration of 125 μg/mL, the extract demonstrated significant inhibition of fungal growth after 6 hours. The combination of gallic acid or extract with nystatin did not exhibit synergistic or antagonistic effect. Furthermore, the extract did not induce cytotoxicity to a human cell line. The extract of S. brasiliensis demonstrates antifungal activity against Candida, generally exhibiting fungicidal action and capacity to inhibit biofilm formation as well as reduce mature biofilms. Additionally, the extract showed low cytotoxicity to human cells.
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Candida albicans is associated with serious infections in immunocompromised patients. Terpenes are natural-product derivatives, widely studied as antifungal alternatives. In a previous study reported by our group, the antifungal activity of α-pinene against C. albicans was verified; α-pinene presented an MIC between 128-512 µg/mL. In this study, we evaluate time-kill, a mechanism of action using in silico and in vitro tests, anti-biofilm activity against the Candida albicans, and toxicity against human cells (HaCaT). Results from the molecular-docking simulation demonstrated that thymidylate synthase (-52 kcal mol-1), and δ-14-sterol reductase (-44 kcal mol-1) presented the best interactions. Our in vitro results suggest that α-pinene's antifungal activity involves binding to ergosterol in the cellular membrane. In the time-kill assay, the antifungal activity was not time-dependent, and also inhibited biofilm formation, while rupturing up to 88% of existing biofilm. It was non-cytotoxic to human keratinocytes. Our study supports α-pinene as a candidate to treat fungal infections caused by C. albicans.
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The gaining popularity of tobacco and nicotine delivery products, such as electronic cigarettes (e-cigarettes) being perceived as relatively safe is of a medical concern. The long-term safety of these new products remains uncertain for oral health. In this study, in vitro effects of e-liquid were assessed in a panel of normal oral epithelium cell lines (NOE and HMK), oral squamous cell carcinoma (OSCC) human cell lines (CAL27 and HSC3), and a mouse oral cancer cell line (AT84) using cell proliferation, survival/cell death, and cell invasion assays. In addition, signaling pathways underlying the pro-invasive activity of e-cigarettes were evaluated by gene and protein expression analysis. We demonstrated that e-liquid promotes proliferation and anchorage-independent growth of OSCC and induces morphological changes associated with enhanced motility and invasive phenotypes. Furthermore, e-liquid-exposed cells express significantly reduced cell viability, regardless of e-cigarette flavour content. At the gene expression level, e-liquid induces changes in gene expression consistent with epithelial to mesenchymal transition (EMT) revealed by reduced expression of cell epithelial markers such as E-cadherin and enhanced expression of mesenchymal proteins like vimentin and B-catenin seen both in OSCC cell lines and normal oral epithelium cells. In summary, the ability of e-liquid to induce proliferative and invasive properties along the activation of the EMT process can contribute to the development of tumorigenesis in normal epithelial cells and promote aggressive phenotype in pre-existing oral malignant cells.
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Carcinoma de Células Escamosas , Sistemas Electrónicos de Liberación de Nicotina , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Animales , Ratones , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Transición Epitelial-Mesenquimal , Neoplasias de la Boca/genética , Células EpitelialesRESUMEN
STATEMENT OF PROBLEM: Stone casts are subject to contamination, but whether disinfectants incorporated into the stone are effective is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the antimicrobial activity and the mechanical and surface properties of self-disinfecting gypsum (SDG) and gypsum mixed with 2% chlorhexidine (GCHX). MATERIAL AND METHODS: Antimicrobial action was evaluated using the diffusion-disk technique on Streptococcus aureus and Candida albicans 1 hour and 24 hours after pouring the gypsum. The groups were SDG, GCHX, a positive control (PC) of gypsum mixed with distilled water, and a negative control (NC) of filter paper disk soaked with 2% chlorhexidine; n=8. Inhibition halos were measured using the ImageJ software program and statistically analyzed using the repeated measures mixed ANOVA with time×group interaction. Compressive strength (CS) in MPa and surface roughness (SR) in µm (parameters: Ra - roughness average; and Sa - 3-dimensional (3D) arithmetic mean of the surface profile) tests were performed to characterize the specimens (evaluated groups: SDG, GCHX, and PC; n=10). CS data were analyzed by a 2-way ANOVA with time×group interaction, and SR data by a 1-way ANOVA (α=.05). RESULTS: For S aureus, there were differences between GCHX and SDG at 1 hour and 24 hours (P<.05), but no significant differences were found for C albicans (P>.05). GCHX was better than PC, except for C albicans, and showed a reduction in CS when compared with PC and SDG (P<.05) at all time intervals. The SR of GCHX increased (Ra:1.76, Sa:2.08) when compared with PC (Ra:0.89, Sa:1.12) and SDG (Ra:1.03, Sa:1.35) (Ra: P<.004 and Sa: P<.001). CONCLUSIONS: The antimicrobial activity of GCHX against S aureus was better than that of SDG, but neither had an effect against C albicans. As for CS and SR, GCHX presented a decrease in properties when compared with PC and SDG but was within the American Dental Association #25 specification values.
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Sulfato de Calcio , Desinfectantes , Clorhexidina/farmacología , Clorhexidina/uso terapéutico , Propiedades de Superficie , Ensayo de MaterialesRESUMEN
Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment's immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC.
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Gastric cancer is the fifth most common and fourth type to cause the highest mortality rates worldwide. The leading cause is related to Helicobacter pylori (H. pylori) infection. Unfortunately, current treatments have low success rates, highlighting the need for alternative treatments against carcinogenic agents, specifically H. pylori. Noteworthy, natural origin products contain pharmacologically active metabolites such as flavonoids, with potential antimicrobial applications. Objective: This article overviews flavonoid-rich extracts' biological and pharmacological activities. It focuses on using these substances against Helicobacter pylori infection to prevent gastric cancer. For this, PubMed and Science Direct databases were searched for studies that reported the activity of flavonoids against H. pylori, published within a 10-year time frame (2010 to August 2020). It resulted in 1,773 publications, of which 44 were selected according to the search criteria. The plant family primarily found in publications was Fabaceae (9.61%). Among the flavonoids identified after extraction, the most prevalent were quercetin (19.61%), catechin (13.72), epicatechin (11.76), and rutin (11.76). The potential mechanisms associated with anti-H. pylori activity to the extracts were: inhibition of urease, damage to genetic material, inhibition of protein synthesis, and adhesion of the microorganism to host cells. Conclusion: Plant extracts rich in flavonoids with anti-H. pylori potential proved to be a promising alternative therapy source, reinforcing the relevance of studies with natural products.
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This in vitro study aimed to evaluate the overall mechanical properties of resin infiltrants doped with bioactive nanofibers and their ability in inhibiting enamel demineralization or achieving remineralization of the adjacent enamel to white spots. A commercial resin infiltrant (ICON, DMG) was doped with hybrid inorganic-organic nanofibers and analyzed for degree of conversion (DC, n = 3) and surface hardness (SH, n = 6). Subsequently, enamel specimens (6 × 4 × 2 mm3) were prepared and submitted to a demineralizing/remineralizing process to produce a subsurface caries-like lesion. The specimens were treated with one of the following materials: ICON infiltrant, DMG (control); ICON + nanofibers of poly-lactic acid (PLA)-filled with silica (PLA-SiO2); ICON + nanofibers of (PLA)-filled with calcium incorporated into a silica network (SiO2-CaP). Then, the specimens were subjected to a pH-cycling demineralizing/remineralizing model for 7 days at 37 °C. The %ΔSH change (after treatment), %SH loss and %SH recovery (after pH-cycling regimen) were calculated after SH evaluation (n = 9/group). The Ca/P weight ratio before and after pH-cycling regimen was evaluated through SEM/EDX. The results of DC were analyzed through the T-test (p < 0.05). ANOVA followed by Tukey's test (p < 0.05) was performed for hardness and EDX. A significant SH increase was observed in the ICON/SiO2CaP group (p < 0.05). The ICON/PLA-SiO2 presented higher DC values than the control group (p = 0.043). All groups presented significant difference in %ΔSH (p < 0.05), although the specimens treated with ICON/SiO2CaP presented greater values. Regarding the %SHL and %SHR, the ICON/SiO2CaP and ICON/PLA-SiO2 were significantly different compared to the control group (p < 0.001). However, no difference was observed between the ICON/SiO2CaP and ICON/PLA-SiO2. The Ca/P ratio showed that the ICON/SiO2CaP and ICON/PLA-SiO2 after the pH-cycling regimen differed from sound enamel and modified infiltrants before pH-cycling. In conclusion, tailored hybrid nanofibers may be incorporated into enamel resin infiltrants without compromise the mechanical properties of such experimental materials. These latter can inhibit the demineralization of enamel and increase its hardness during pH-clycling challange.
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Caries Dental , Nanofibras , Dureza , Humanos , Dióxido de Silicio , Propiedades de SuperficieRESUMEN
This study evaluated the in vitro antimicrobial and immunomodulatory action of crude extracts from Anacardium occidentale L. (cashew tree) leaves and bark, and to determine their toxicity to peripheral-blood mononuclear cells (PBMCs) and to zebrafish embryos and larvae. Chemical analysis of extracts was performed by proton nuclear magnetic resonance (1H-NMR). The antibacterial activity was evaluated against selected bacteria strains by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Cytotoxicity of the extracts was assessed using resazurin method, while the effect on production of ROS by PMN leukocytes was measured by luminol. Embryotoxicity to zebrafish was assessed using the fish embryo acute toxicity test (FET) and quantification of toxicity marker enzymes (AChE, LDH, and GST). 1H-NMR results showed anacardic acid as the main component of the extracts. All bacterial species tested were sensitive to the extracts, with MICs ranging from 312.5 to 10,000 µg/mL. Streptococcus mutans and Escherichia coli were the most susceptible species. The extracts promoted cell viability above 75% at concentrations from 1.25 to 80 µg/mL. Both extracts reduced zymosan-induced ROS (p < 0.05) at concentrations of 1, 8, and 80 µg/mL compared to the control. In vivo, there were embryotoxic effects in zebrafish embryos exposed to both extracts through the presence of lethal and sublethal endpoints. The samples also acted by inhibiting the activities of biomarker enzymes. The A. occidentale L. bark and leaf extracts showed antimicrobial potential and modulated ROS production in vitro, but these also showed embryotoxic effects to zebrafish.
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Anacardium , Animales , Anacardium/química , Pez Cebra , Luminol , Zimosan , Protones , Especies Reactivas de Oxígeno , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Antibacterianos/toxicidad , Antibacterianos/química , Bacterias , Antiinflamatorios , LeucocitosRESUMEN
Chagas Disease, also known as American trypanosomiasis, is a Neglected Tropical Disease that affects around seven million people, especially in Latin America. Noteworthy, there has been an increase in the numbers of case reports in non-endemic areas, such as North America, Europe, Japan, and Australia. The disease is a vector-borne disease caused by the pathogen Trypanosoma cruzi being transmitted by infected bugs. It is known that about forty percent of infected patients develop cardiac, digestive, or neurological alterations. There are only two drugs currently used for treatment, benznidazole and nifurtimox. However, both therapeutic regimens present several limitations, such as toxicity, mutagenicity and low efficiency during the chronic phase. Some reports in the literature point to the occurrence of parasite resistance. To overcome these limitations, the bioprospection of novel molecules as alternatives is one of the major goals to improve therapeutic success in this chronic disease. Bioprospecting active metabolites from natural resources might bring new hopes for disease control and parasite elimination. Here we summarize the most recent advances to identify and test Algae, Bacteria and Fungi-derived bioactive compounds with trypanocidal activity using experimental models, in vitro testing and in silico approaches.
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Enfermedad de Chagas , Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Bacterias , Enfermedad de Chagas/tratamiento farmacológico , Hongos , Humanos , Nifurtimox/uso terapéutico , Nitroimidazoles/uso terapéutico , Tripanocidas/farmacología , Tripanocidas/uso terapéuticoRESUMEN
This study evaluated the effects of flours from four different sweet potato root (SPR) varieties, being two with white peel and two with purple peel, on the composition and metabolic activity of human colonic microbiota in vitro. The capability of these SPR flours (20 g/L) to cause alterations in relative abundance of different bacterial groups found as part of human colonic microbiota, as well as in lactic acid and short-chain fatty acid production was evaluated during 48 hr of an in vitro colonic fermentation. The SPR flours were submitted to a simulated gastrointestinal digestion prior to use in experiments. The four SPR flours increased the relative abundance of Lactobacillus/Enterococcus (range: 0.49-4.48%) and Bifidobacterium (range: 0.32-3.27%) and decreased the relative abundance of Bacteroides/Prevotella (range: 0.29-7.49%), Clostridium histolyticum (range: 0.15-2.08%), and Eubacterium rectale/Clostridium coccoides (range: 0.28-3.86%) during the 48 hr of colonic fermentation. The four SPRF flours had positive prebiotic indexes (> 0.38) after 24 and 48 hr of colonic fermentation, reinforcing the occurrence of selective stimulatory effects on colonic microbiota. An increased metabolic activity of human colonic microbiota was caused by tested SPR flours, which was evidenced by decreased pH (range: 3.20-3.83) and increased lactic acid and short chain fatty acid production during the 48 hr of colonic fermentation. The four examined SPR flours were capable of causing positive alterations in composition and driving the metabolic activity of human colonic microbiota during in vitro colonic fermentation, which should be linked to their prebiotic properties. PRACTICAL APPLICATION: The four examined sweet potato root flours (SPRF) caused beneficial alterations in composition besides of driving the metabolic activity of human colonic microbiota in vitro. These results characterize the examined SPRF as candidates for use as prebiotic ingredients by food industry for formulation of value-added functional foods or dietary supplements.
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Ipomoea batatas , Microbiota , Clostridiales , Heces/química , Fermentación , Harina , Humanos , Prebióticos/análisisRESUMEN
Head and neck squamous cell carcinoma (HNSCC), a prevalent cancer worldwide, has a high incidence of loco-regional dissemination, frequent recurrence, and lower 5-year survival rates. Current gold standard treatments for advanced HNSCC rely primarily on radiotherapy and chemotherapy but with limited efficacy and significant side effects. In this study, we characterized a novel 5-fluorouracil (5-FU) carrier composed of chitosan solution (CS) and polycaprolactone (PCL) microparticles (MPs) in HNSCC preclinical models. The designed MPs were evaluated for their size, morphology, drug entrapment efficiency (EE%) and in vitro drug release profile. The anti-cancer activity of 5-FU-loaded particles was assessed in HNSCC human cell lines (CAL27 and HSC3) and in a preclinical mouse model (AT84) utilizing cell proliferation and survival, cell motility, and autophagy endpoints. The results demonstrated a 38.57 % in 5-FU entrapment efficiency associated with reduced 5-FU in vitro release up to 96 h post-exposure. Furthermore, CS-decorated PCL MPs were able to promote a significant inhibition of cancer cell proliferation based on the metabolic and colony formation assays, in comparison to controls. In contrast, CS-decorated PCL MPs did not influence the pharmacological efficacy of 5-FU to inhibit in vitro cancer cell migration. Last, cell protein analysis revealed a significant increase of autophagy and cell death evaluated by LC3-II expression and PARP1 cleavage, respectively. In summary, these results support the potential utility of CS-decorated PCL MPs as an effective 5-FU-delivery carrier to improve HNSCC therapeutic management.
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Antimetabolitos Antineoplásicos/farmacología , Quitosano/química , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Nanopartículas/administración & dosificación , Poliésteres/química , Animales , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/química , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quitosano/administración & dosificación , Liberación de Fármacos , Fluorouracilo/administración & dosificación , Fluorouracilo/química , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Ratones , Nanopartículas/química , Tamaño de la Partícula , Poliésteres/administración & dosificaciónRESUMEN
AIM: It was analyzed the efficacy of mouthwash and spray containing essential oil (EO) of Cinnamomum zeylanicum Blume for the treatment of oral candidiasis. METHODS AND RESULTS: A randomized, controlled, and blinded clinical trial was conducted with 36 individuals (probabilistic sample) with oral candidiasis who were divided into two treatment groups: C. zeylanicum (0.5 mg/mL), n = 18; nystatin (100,000IU/mL), n = 18. The efficacy of the products was evaluated by two parameters: (a) clinical evolution recorded by calibrated examiners (Kappa = 0.822) according to Newton's classification and (b) reduction of colony-forming units/mL. Mycological and clinical parameters were analyzed before and at 15 days after treatment. Clinical examination of the mucosa showed that C. zeylanicum (p < 0.0339) and nystatin (p < .0139) had efficacy, resulting in a reduction of signs and symptoms (Mann-Whitney test). Mycological analysis showed that C. zeylanicum caused a reduction of 61% and 33% of Candida spp., isolates oral mucosa and dentures, respectively. Candida tropicalis strains were eliminated after C. zeylanicum, in both sites. The participants reported a pleasant taste and few product-related complaints. CONCLUSION: C. zeylanicum EO and nystatin exhibited clinical efficacy, according to the Newton classification, and reducing in Candida spp. The clinical trial has been registered (Registration number: NBR-33s6 × 5, ensaiosclinicos.gov.br).
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Candidiasis Bucal , Aceites Volátiles , Antifúngicos/uso terapéutico , Candidiasis Bucal/tratamiento farmacológico , Cinnamomum zeylanicum , Humanos , Nistatina/uso terapéutico , Aceites Volátiles/uso terapéuticoRESUMEN
Non-plaque-induced lesions may occur on the gingiva as medical disorders or manifestations of systemic conditions. Scabies is a parasitic infection caused by Sarcoptes scabiei. Here, we present the first case of oral scabies reported in the literature located on the gingiva in a 43-year-old woman. She was admitted to the hospital complaining of an ulcerative lesion on the gingiva with unknown duration, with a suggestive diagnosis of pemphigoid. A diagnosis of scabies infestation was made based on the visualization of eggs and larvae/nymph forms. The treatment consisted of 100 mg of ivermectin (three times per day for 15 days), supplemental oral hygiene with chlorhexidine, and extensive cleaning. The follow-up was made 30 days after treatment with ivermectin. The patient did not report side effects, with skin and oral lesions completely healed. Based on this, we need to perform a thoughtful ectoscopy examination and be alert to signs that indicate unusual causes to diagnose correctly and choose the appropriate treatment.
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Gingivitis/parasitología , Úlceras Bucales/parasitología , Escabiosis/diagnóstico , Escabiosis/patología , Adulto , Antiparasitarios/uso terapéutico , Femenino , Humanos , Ivermectina/uso terapéutico , Escabiosis/tratamiento farmacológicoRESUMEN
The aim of this study was to develop polymeric nanofibers for controlled administration of Amphotericin B (AmpB), using the solution centrifugation technique, characterizing its microstructural and physical properties, release rate, and activity against Leishmania and Candida species. The core-shell nanofibers incorporated with AmpB were synthesized by Solution Blow Spinning (SBS) and characterized by scanning electron microscopy (SEM), differential scanning calorimetry, X-Ray diffraction, and drug release assay. In vitro leishmanicidal and antifungal activity were also evaluated. Fibrous membranes with uniform morphology and smooth surfaces were produced. The intensity of the diffraction peaks becomes slightly more pronounced, assuming the increased crystallization in PLA/PEG at high AmpB loadings. Drug release occurred and the solutions with nanofibers to encourage greater incorporation of AmpB showed a higher concentration. In the results of the experiment with promastigotes, the wells treated with nanofibers containing concentrations of AmpB at 0.25, 0.5, and 1%, did not have any viable cells, similar to the positive control. Various concentrations of AmpB improved the inhibition of fungal growth. The delivery system based on PLA/PEG nanofibers was properly developed for AmpB, presenting a controlled release and a successful encapsulation, as well as antifungal and antileishmanial activity.
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The influence of antimoniate treatment on specific anti-protozoan T-cell responses was evaluated in a 48-year-old male patient diagnosed with mucosal leishmaniasis and Chagas disease infection. Before and after treatment, PBMC (peripheral blood mononuclear cells) were cultured in the absence or presence of Leishmania braziliensis or Trypanosoma cruzi live parasites, their soluble antigens, or PHA (phytohaemagglutinin). Cytokines were measured and Treg (T regulatory) cell percentages were quantified. Before treatment, PBMC were able to produce higher amounts of TNF-α, IL-6 (Interleukin-6), and IL-10 (Interleukin-10) but lower amounts of IL-12 (Interleukin-12) in response to culture stimulation. However, after treatment, there was a down-modulation of TNF-α, IL-6, and IL-10 cytokines but an up-modulation in IL-12 production. PBMC had the ability to produce TNF-α only against live parasites or PHA. There was an overall decrease of circulating Treg cells after treatment. In mixed Leishmaniasis and Chagas disease infection, treatment with antimoniate could modulate immune responses toward a more protective profile to both diseases.
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Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that could be used for diagnosis, vaccine, and drugs targets against T. cruzi using reverse vaccinology and molecular docking. The genomes of 28 T. cruzi strains available in GenBank (NCBI) were used to obtain the genomic core. Then, subtractive genomics was carried out to identify nonhomologous genes to the host in the core. A total of 2630 conserved proteins in 28 strains of T. cruzi were predicted using OrthoFinder and Diamond software, in which 515 showed no homology to the human host. These proteins were evaluated for their subcellular localization, from which 214 are cytoplasmic and 117 are secreted or present in the plasma membrane. To identify the antigens for diagnosis and vaccine targets, we used the VaxiJen software, and 14 nonhomologous proteins were selected showing high binding efficiency with MHC I and MHC II with potential for in vitro and in vivo tests. When these 14 nonhomologous molecules were compared against other trypanosomatids, it was found that the retrotransposon hot spot (RHS) protein is specific only for T. cruzi parasite suggesting that it could be used for Chagas diagnosis. Such 14 proteins were analyzed using the IEDB software to predict their epitopes in both B and T lymphocytes. Furthermore, molecular docking analysis was performed using the software MHOLline. As a result, we identified 6 possible T. cruzi drug targets that could interact with 4 compounds already known as antiparasitic activities. These 14 protein targets, along with 6 potential drug candidates, can be further validated in future studies, in vivo, regarding Chagas disease.
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Antiprotozoarios/farmacología , Enfermedad de Chagas/diagnóstico , Genoma de Protozoos , Vacunas Antiprotozoos/genética , Trypanosoma cruzi/genética , Antígenos de Protozoos/genética , Antígenos de Protozoos/inmunología , Antiprotozoarios/química , Biomarcadores/análisis , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/prevención & control , Descubrimiento de Drogas , Genómica , Humanos , Simulación del Acoplamiento Molecular , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Vacunas Antiprotozoos/inmunología , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/inmunologíaRESUMEN
Abstract Covid-19 is a respiratory disease caused by the SARS-CoV-2 virus. The high rate of contagion and the spread of the virus in the population make the early detection of the pathogen the means for the adequate targeting of infection control measures. WHO directs sample collection on upper respiratory specimens, including nasopharyngeal and oropharyngeal swab or wash in ambulatory patients, as well as lower respiratory specimens: sputum and/or endotracheal aspirate or bronchoalveolar lavage, in addition to citing blood and feces. Among the various sample collection methods, saliva has been investigated and reported as a potential source for diagnosis. Thus, we propose to evaluate the current scenario, based on recent publications on the perspective of detecting SARS-CoV-2 in saliva as a diagnostic method for Covid-19. The detection of SARS-CoV-2 through saliva seems to be very promising, although obstacles such as the technique and the location of the collection and the sample size of the research carried out so far may present a limitation for its use. The current scenario presents saliva as a reliable method for the detection of SARS-CoV-2, due to the ease of obtaining the samples, the possibility of self-collection, low cost because there is no need to use specific equipment, in addition to reducing the risk of transmission for health professionals.