RESUMEN
Despite the severe impact of uncommon yeast fungal infections and the pressing need for more research on the topic, there are still few studies available on the identification, epidemiology, and susceptibility profile of those pathogens. The aims of the current study were to define the profile of uncommon yeast species at Fattouma Bourguiba University Hospital using phenotypic, molecular, and proteomic methods and to study their antifungal susceptibility profile. Pre-identified uncommon yeast species were collected from 2018 to 2021. These isolates were further identified using phenotypic methods (ID32C® system and Vitek2® YST), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and sequencing. The antifungal susceptibility profile was studied using the reference CLSI broth microdilution method. In total, 30 strains were collected during the study period. Referring to the sequencing, the most isolated uncommon species were Saprochaete capitata, Candida lusitaniae, Candida kefyr, Candida inconspicua, and Candida guilliermondii. A total of 90% of isolates were correctly identified by MALDI-TOF MS compared to 76.7% and 63.3% by ID32® C and VITEK® 2 YST, respectively. The isolated species showed variable responses to antifungals. Candida guilliermondii showed increased azole minimum inhibitory concentrations. Misidentification of uncommon yeast species was common using commercial phenotypic methods. The high percentage of concordance of MALDI-TOF results with sequencing highlights its high performance and usefulness as a routine diagnosis tool.
There is still little information on the epidemiology of uncommon emergent yeasts, although their implication in severe diseases and mainly invasive infections. Thus, the importance of an accurate identification and antifungal susceptibility testing for a better monitoring of related infections.
Asunto(s)
Antifúngicos , Hospitales Universitarios , Pruebas de Sensibilidad Microbiana , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Levaduras , Humanos , Antifúngicos/farmacología , Túnez , Levaduras/efectos de los fármacos , Levaduras/aislamiento & purificación , Levaduras/clasificación , Levaduras/genética , Micosis/microbiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Niño , Candida/efectos de los fármacos , Candida/clasificación , Candida/aislamiento & purificación , Candida/genética , Preescolar , Adolescente , Adulto Joven , Anciano , Farmacorresistencia FúngicaRESUMEN
Zoonotic yeast species have been implicated in disease development in both humans and cats. This study analyzed the yeast mycobiota present in feline facial hair and human nails and explored potential interspecies associations. A total of 118 biological specimens were examined, including 59 feline facial hair and 59 human nail samples. DNA extraction and DNA sequencing were performed to identify the specific yeast species. The most predominant yeast species in humans and cats were selected for antifungal susceptibility testing (itraconazole, ketoconazole, miconazole, and terbinafine). The findings unveiled diverse yeast species in cats and humans. Malassezia pachydermatis (45.8%) and Malassezia furfur (30.5%) were the most common yeast species in cats and humans, respectively. However, no significant correlation was detected between the yeast species identified in cats and their owners residing in the same household (p > 0.05). Miconazole exhibited the highest minimum inhibitory concentrations (MICs) against Malassezia pachydermatis and Malassezia furfur in both cat and human isolates, whereas terbinafine showed the lowest MICs against most Malassezia pachydermatis and Malassezia furfur in both cat and human isolates. Diverse yeast species in cat facial hair and human nails suggest possible cross-contamination among humans, pets, and environments.
Asunto(s)
Antifúngicos , Pruebas de Sensibilidad Microbiana , Uñas , Gatos , Humanos , Antifúngicos/farmacología , Animales , Uñas/microbiología , Malassezia/efectos de los fármacos , Malassezia/genética , Malassezia/aislamiento & purificación , Cabello/microbiología , Levaduras/efectos de los fármacos , Levaduras/aislamiento & purificación , Levaduras/genética , Terbinafina/farmacología , Miconazol/farmacología , Masculino , Pelaje de Animal/microbiología , FemeninoRESUMEN
Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited, and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor, and outcome. In addition, a candidemia group, including patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole, and amphotericin B were ≤ 2 µg/ml, and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs, and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters, and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species was the problem, particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.
Among all fungemia episodes, hematological malignancies, immunosuppressive therapy, neutropenia, and preexposure to antifungals were risk factors for non-Candida yeast fungemia; diabetes mellitus, urinary catheters, and total parenteral nutrition were risks for candidemia.
Asunto(s)
Antifúngicos , Candida , Candidemia , Fungemia , Pruebas de Sensibilidad Microbiana , Centros de Atención Terciaria , Humanos , Estudios Retrospectivos , Centros de Atención Terciaria/estadística & datos numéricos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candida/clasificación , Fungemia/microbiología , Fungemia/epidemiología , Fungemia/tratamiento farmacológico , Adulto , Candidemia/microbiología , Candidemia/epidemiología , Candidemia/tratamiento farmacológico , Levaduras/aislamiento & purificación , Levaduras/efectos de los fármacos , Levaduras/clasificación , Anciano de 80 o más Años , Fluconazol/farmacología , Fluconazol/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: The aim was to systematically review clinical studies that investigated the efficacy of antimicrobial photodynamic therapy (aPDT) in reducing oral yeasts growth (OYG) in individuals wearing implant overdentures (IO). METHODS: The focused question was "Is aPDT effective in reducing OYG in patients wearing IO?" Literature search was performed in accordance with PRISMA guidelines. Indexed databases were searched without time and language restrictions up to and including January 2024. Clinical studies were included; and letters to the Editor, case-reports/case-series, perspectives/commentaries, in-vitro/ex-vivo studies, studies on animal models and expert opinions were excluded. The risk of bias was also assessed. RESULTS: Two clinical studies were included and processed for data extraction. The study population comprised of 100 (mean age: 58.5 years) and 53 (mean age: 58.5 years) individuals. The numbers of males and females included in these studies ranged between 33 and 35 males and 18-67 females, respectively. In both studies, follow-up evaluations were performed after 60 days. In both studies, aPDT was performed using a 660 nm diode laser at a power of 100 mW and using methylene-blue as photosensitizer. Results from both studies showed that aPDT is effective in significantly reducing oral yeasts CFU/ml and improvement of OHRQoL of individuals using IO. CONCLUSION: The aPDT is useful in reducing OYG on IO; however, further well-designed and power-adjusted studies are needed in this area of research.
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Prótesis de Recubrimiento , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fotoquimioterapia/métodos , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Azul de Metileno/farmacología , Azul de Metileno/uso terapéutico , Láseres de Semiconductores/uso terapéutico , Levaduras/efectos de los fármacos , Ensayos Clínicos como AsuntoRESUMEN
This research paper presents a novel approach to the green synthesis of silver nanoparticles (AgNPs) using viticultural waste, allowing to obtain NP dispersions with distinct properties and morphologies (monodisperse and polydisperse AgNPs, referred to as mAgNPs and pAgNPs) and to compare their biological activities. Our synthesis method utilized the ethanolic extract of Vitis vinifera pruning residues, resulting in the production of mAgNPs and pAgNPs with average sizes of 12 ± 5 nm and 19 ± 14 nm, respectively. Both these AgNPs preparations demonstrated an exceptional stability in terms of size distribution, which was maintained for one year. Antimicrobial testing revealed that both types of AgNPs inhibited either the growth of planktonic cells or the metabolic activity of biofilm sessile cells in Gram-negative bacteria and yeasts. No comparable activity was found towards Gram-positives. Overall, pAgNPs exhibited a higher antimicrobial efficacy compared to their monodisperse counterparts, suggesting that their size and shape may provide a broader spectrum of interactions with target cells. Both AgNP preparations showed no cytotoxicity towards a human keratinocyte cell line. Furthermore, in vivo tests using a silkworm animal model indicated the biocompatibility of the phytosynthesized AgNPs, as they had no adverse effects on insect larvae viability. These findings emphasize the potential of targeted AgNPs synthesized from viticultural waste as environmentally friendly antimicrobial agents with minimal impact on higher organisms.
Asunto(s)
Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Plata , Vitis , Plata/farmacología , Plata/química , Plata/metabolismo , Nanopartículas del Metal/química , Animales , Humanos , Vitis/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Tamaño de la Partícula , Tecnología Química Verde , Bacterias Gramnegativas/efectos de los fármacos , Bombyx , Biopelículas/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Larva/efectos de los fármacos , Levaduras/efectos de los fármacosRESUMEN
Formaldehyde and acetaldehyde are reactive small molecules produced endogenously in cells as well as being environmental contaminants. Both of these small aldehydes are classified as human carcinogens, since they are known to damage DNA and exposure is linked to cancer incidence. However, the mutagenic properties of formaldehyde and acetaldehyde remain incompletely understood, at least in part because they are relatively weak mutagens. Here, we use a highly sensitive yeast genetic reporter system featuring controlled generation of long single-stranded DNA regions to show that both small aldehydes induced mutational patterns characterized by predominantly C/G â A/T, C/G â T/A, and T/A â C/G substitutions, each in similar proportions. We observed an excess of C/G â A/T transversions when compared to mock-treated controls. Many of these C/G â A/T transversions occurred at TC/GA motifs. Interestingly, the formaldehyde mutational pattern resembles single base substitution signature 40 from the Catalog of Somatic Mutations in Cancer. Single base substitution signature 40 is a mutational signature of unknown etiology. We also noted that acetaldehyde treatment caused an excess of deletion events longer than 4 bases while formaldehyde did not. This latter result could be another distinguishing feature between the mutational patterns of these simple aldehydes. These findings shed new light on the characteristics of 2 important, commonly occurring mutagens.
Asunto(s)
Acetaldehído , Neoplasias , Humanos , Acetaldehído/toxicidad , Análisis Mutacional de ADN , Formaldehído/toxicidad , Mutágenos/toxicidad , Mutación , Levaduras/efectos de los fármacos , Levaduras/genéticaRESUMEN
The essential oils of three specimens of Myrcia multiflora (A, B and C) and Eugenia florida were extracted by hydrodistillation, and the chemical compositions from the essential oils were identified by gas chromatography and flame ionization detection (CG/MS and CG-FID). The fungicide potential of the EOs against five fungicide yeasts was assessed: Candida albicans INCQS-40175, C. tropicalis ATCC 6258, C. famata ATCC 62894, C. krusei ATCC 13803 and C. auris IEC-01. The essential oil of the specimen Myrcia multiflora (A) was characterized by the major compounds: α-bulnesene (26.79%), pogostol (21.27%) and δ-amorphene (6.76%). The essential oil of the specimen M. multiflora (B) was rich in (E)-nerolidol (44.4%), (E)-γ-bisabolene (10.64%) and (E,E)-α-farnesene (8.19%), while (E)-nerolidol (92.21%) was the majority of the specimen M. multiflora (C). The sesquiterpenes seline-3,11-dien-6-α-ol (12.93%), eremoligenol (11%) and γ-elemene (10.70%) characterized the chemical profile of the EOs of E. florida. The fungal species were sensitive to the essential oil of M. multiflora (B) (9-11 mm), and the lowest inhibitory concentration (0.07%) was observed in the essential oil of M. multiflora (A) against the yeasts of C. famata. Fungicidal action was observed in the essential oils of M. multiflora (A) against C. famata, with an MIC of 0.78 µL/mL and 3.12 µL/mL; C. albicans, with an MFC of 50 µL/mL and M. multiflora (C) against C. albicans; and C. krusei, with a MFC of 50 µL/mL.
Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Eugenia/química , Myrtaceae/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Antiinfecciosos/farmacología , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología , Análisis de Componente Principal , Levaduras/efectos de los fármacosRESUMEN
Heavy metals act as cofactors for several microbial enzymes and are required in low concentrations for the proper biological functioning of yeasts. Because concentrations beyond the permitted threshold can damage a cell's functionality and viability, metal tolerance in yeasts towards such heavy metals is therefore desirable during fermentation. Tyrosol, a quorum-sensing molecule in yeasts, protects yeasts from oxidative stress induced by various factors, but the performance of the molecule under heavy metal-induced stress is not known. In this investigation, the metal tolerance of four species of endemic yeasts from northeast India, Wickerhamomyces anomalus, Candida tropicalis, Saccharomyces cerevisiae and Candida glabrata, isolated from traditional starter culture cakes, was tested towards zinc (Zn+2), manganese (Mn+2), cobalt (Co+2) and copper (Cu+2) in the presence and absence of tyrosols retrieved from these isolates. The decreasing order of the tolerance of isolates was found to be Mn+2 > Zn+2 > Co+2 > Cu+2. Under the influence of tyrosols, isolates showed enhanced growth at their upper metal tolerance limit. Candida tropicalis showed enhanced growth (2-48-fold, P < 0.0001) in all the tested metal consisting medium (2 mM Zn+2, 5 mM Mn+2, 2 mM Co+2 and 1 mM Cu+2), while W. anomalus, C. glabrata and S. cerevisiae showed increased growth (3-17-fold, P < 0.0001) in Zn+2 (2 mM), Mn+2 (5 mM) and Cu+2 (1 mM) augmented medium. The overall result suggests that tyrosol exerts a protective effect under heavy metal-induced stress, which could be useful in enhancing the quality of fermented products.
Asunto(s)
Metales Pesados , Alcohol Feniletílico/análogos & derivados , Cobre/farmacología , Metales Pesados/toxicidad , Alcohol Feniletílico/aislamiento & purificación , Alcohol Feniletílico/farmacología , Estrés Fisiológico/efectos de los fármacos , Levaduras/efectos de los fármacos , Levaduras/crecimiento & desarrollo , Zinc/toxicidadRESUMEN
4,5,6,7-Tetrabromo-1H-benzotriazole is widely used as the reference ATP-competitive inhibitor of protein kinase CK2. Herein, we study its new analogs: 5,6-diiodo- and 5,6-diiodo-4,7-dibromo-1H-benzotriazole. We used biophysical (MST, ITC) and biochemical (enzymatic assay) methods to describe the interactions of halogenated benzotriazoles with the catalytic subunit of human protein kinase CK2 (hCK2α). To trace the biological activity, we measured their cytotoxicity against four reference cancer cell lines and the effect on the mitochondrial inner membrane potential. The results obtained lead to the conclusion that iodinated compounds are an attractive alternative to brominated ones. One of them retains the cytotoxicity against selected cancer cell lines of the reference TBBt with a smaller side effect on mitochondrial activity. Both iodinated compounds are candidate leaders in the further development of CK2 inhibitors.
Asunto(s)
Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Triazoles/farmacología , Biomarcadores , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Análisis Espectral , Triazoles/química , Levaduras/efectos de los fármacos , Levaduras/metabolismoRESUMEN
Silymarin is known for its hepatoprotective effects. Although there is solid evidence for its protective effects against Amanita phalloides intoxication, only inconclusive data are available for alcoholic liver damage. Since silymarin flavonolignans have metal-chelating activity, we hypothesized that silymarin may influence alcoholic liver damage by inhibiting zinc-containing alcohol dehydrogenase (ADH). Therefore, we tested the zinc-chelating activity of pure silymarin flavonolignans and their effect on yeast and equine ADH. The most active compounds were also tested on bovine glutamate dehydrogenase, an enzyme blocked by zinc ions. Of the six flavonolignans tested, only 2,3-dehydroderivatives (2,3-dehydrosilybin and 2,3-dehydrosilychristin) significantly chelated zinc ions. Their effect on yeast ADH was modest but stronger than that of the clinically used ADH inhibitor fomepizole. In contrast, fomepizole strongly blocked mammalian (equine) ADH. 2,3-Dehydrosilybin at low micromolar concentrations also partially inhibited this enzyme. These results were confirmed by in silico docking of active dehydroflavonolignans with equine ADH. Glutamate dehydrogenase activity was decreased by zinc ions in a concentration-dependent manner, and this inhibition was abolished by a standard zinc chelating agent. In contrast, 2,3-dehydroflavonolignans blocked the enzyme both in the absence and presence of zinc ions. Therefore, 2,3-dehydrosilybin might have a biologically relevant inhibitory effect on ADH and glutamate dehydrogenase.
Asunto(s)
Alcohol Deshidrogenasa/antagonistas & inhibidores , Quelantes/farmacología , Flavonolignanos/farmacología , Silimarina/farmacología , Zinc/aislamiento & purificación , Animales , Glutamato Deshidrogenasa/antagonistas & inhibidores , Caballos , Silibina/farmacología , Levaduras/efectos de los fármacos , Zinc/metabolismoRESUMEN
One of the greatest threats to human and animal health is posed by infections caused by drug-resistant bacterial strains. Therefore, newly synthesised substances are tested for their antimicrobial activity. Carbazole derivatives seem to be promising antibacterial agents. This study aimed at investigating the toxicity and activity of newly synthesised, functionalised carbazole derivative 2 (4-(4-(benzylamino)butoxy)-9H-carbazole) against various microorganisms. Its antimicrobial potential against Gram-positive and Gram-negative bacteria, yeast, and filamentous fungi was examined according to CLSI (Clinical and Laboratory Standards Institute) standards. The tested compound was found to efficiently inhibit the growth of Gram-positive strains. The addition of carbazole derivative 2 at the concentration of 30 µg/mL caused inhibition of bacterial growth by over 95%. Moreover, about 50 and 45% limitation of Pseudomonas aeruginosa and Aspergillus flavus growth was observed in the samples incubated with the addition of 20 and 60 µg/mL of the compound, respectively. Its addition to the microbial cultures caused an increase in the permeability of the cellular membrane. Slight haemolysis of red blood cells was observed after 24-h treatment with carbazole derivative 2. On the other hand, human fibroblasts were found to be more sensitive to its effects. The activity of the tested compound indicates a possibility of its further modification in order to obtain effective drugs, especially against drug-resistant staphylococci.
Asunto(s)
Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Carbazoles/química , Fibroblastos/efectos de los fármacos , Hongos/efectos de los fármacos , Levaduras/efectos de los fármacos , Antiinfecciosos/química , HumanosRESUMEN
Plant cysteine-rich peptides (CRPs) represent a diverse group of molecules involved in different aspects of plant physiology. Antimicrobial peptides, which directly suppress the growth of pathogens, are regarded as promising templates for the development of next-generation pharmaceuticals and ecologically friendly plant disease control agents. Their oligopeptide fragments are even more promising because of their low production costs. The goal of this work was to explore the antimicrobial activity of nine short peptides derived from the γ-core-containing regions of tomato CRPs against important plant and human pathogens. We discovered antimicrobial activity in peptides derived from the defensin-like peptides, snakins, and MEG, which demonstrates the direct involvement of these CRPs in defense reactions in tomato. The CRP-derived short peptides appeared particularly active against the gram-positive bacterium Clavibacter michiganensis, which causes bacterial wilt-opening up new possibilities for their use in agriculture to control this dangerous disease. Furthermore, high inhibitory potency of short oligopeptides was demonstrated against the yeast Cryptococcus neoformans, which causes serious diseases in humans, making these peptide molecules promising candidates for the development of next-generation pharmaceuticals. Studies of the mode of action of the two most active peptides indicate fungal membrane permeabilization as a mechanism of antimicrobial action.
Asunto(s)
Péptidos Antimicrobianos/síntesis química , Péptidos Antimicrobianos/farmacología , Cisteína/química , Oligopéptidos/síntesis química , Oligopéptidos/farmacología , Solanum lycopersicum/química , Secuencia de Aminoácidos , Bacterias/efectos de los fármacos , Técnicas de Química Sintética , Relación Dosis-Respuesta a Droga , Solanum lycopersicum/inmunología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Oligopéptidos/química , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Conformación Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Relación Estructura-Actividad , Levaduras/efectos de los fármacosRESUMEN
The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells.
Asunto(s)
Contaminantes Ambientales/toxicidad , Grafito/toxicidad , Nanoestructuras/toxicidad , Pruebas de Toxicidad/métodos , Toxicogenética/métodos , Células A549 , Análisis por Conglomerados , Ensayo Cometa/métodos , Daño del ADN , Contaminantes Ambientales/química , Grafito/química , Humanos , Microscopía Electrónica de Rastreo/métodos , Nanoestructuras/química , Nanoestructuras/ultraestructura , Oxidación-Reducción/efectos de los fármacos , Espectroscopía de Fotoelectrones/métodos , Proteoma/clasificación , Proteoma/efectos de los fármacos , Proteómica/métodos , Especies Reactivas de Oxígeno/metabolismo , Levaduras/citología , Levaduras/efectos de los fármacos , Levaduras/metabolismoRESUMEN
Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.
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Antineoplásicos Fitogénicos/farmacología , Daño del ADN/efectos de los fármacos , Flavonoides/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Reparación del ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Medicamentos Herbarios Chinos , Regulación de la Expresión Génica , Recombinación Homóloga/efectos de los fármacos , Humanos , Ratones , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Levaduras/efectos de los fármacos , Levaduras/genética , Levaduras/metabolismoRESUMEN
BACKGROUND: Lifestyle factors such as hair length, the frequency of ear cleaning and bathing, age, cat rearing, and sex may contribute to opportunistic yeast infections in the external ear canal of cats. This study aimed to determine the prevalence of commensal yeast organisms in cats' external ear canals, evaluate their predisposing lifestyle factors, and test the susceptibility of Malassezia pachydermatis to antifungal agents. RESULTS: A total of 53 cats (33 male and 20 female) seronegative for feline leukemia virus and feline immunodeficiency virus were enrolled in this study. Their mean age (± standard deviation) was 6.04 (± 3.49) years. Fungal cultures and polymerase chain reaction tests were performed to identify the yeast species derived from the external ear canal. The association between lifestyle factors and the presence of M. pachydermatis was evaluated using Fisher's exact test. The susceptibility of M. pachydermatis to antifungal agents was also analyzed. M. pachydermatis was the most frequently recovered yeast species, with a prevalence of 50.94 % (95 % confidence interval [CI]: 36.84-64.94 %). There was an association between hair length and a positive culture for M. pachydermatis (p = 0.0001). The odds of a negative culture for M. pachydermatis among short-haired cats was 11.67 (95 % CI, 3.22-42.24) times higher than that among long-haired cats (p = 0.0002). There was also an association between the frequency of ear cleaning and the presence of M. pachydermatis (p = 0.007). The odds of a negative culture for M. pachydermatis in cats that were receiving ear cleaning at intervals of ≤ 2 weeks was 5.78 (95 % CI, 1.67-19.94) times greater than that of cats receiving ear cleaning at intervals greater than 2 weeks or never (p = 0.0055). Ranges of minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations for itraconazole, ketoconazole, miconazole, and terbinafine against M. pachydermatis were ≤ 0.063-4 and ≤ 0.063-≥32, ≤ 0.063-8 and 0.125-≥32, ≤ 0.063-≥32 and 0.5-≥32, and ≤ 0.016-1 and 0.125-8 µg/ml, respectively. CONCLUSIONS: M. pachydermatis was the most commonly identified yeast organism in the external ear canal of healthy cats. Hair length and the frequency of ear cleaning played a role in the colonization of M. pachydermatis. The M. pachydermatis isolates had various MIC levels for common fungicides.
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Antifúngicos/farmacología , Enfermedades de los Gatos/microbiología , Conducto Auditivo Externo/microbiología , Levaduras/aislamiento & purificación , Pelaje de Animal , Animales , Gatos , Femenino , Malassezia/efectos de los fármacos , Malassezia/aislamiento & purificación , Masculino , Prevalencia , Levaduras/efectos de los fármacosRESUMEN
Tailoring nanomaterials with tunable properties is of great importance to develop multifunctional candidates in the biomedical field. In the present study, we aimed to develop a promising nano-hybrid system composed of chitosan (CS) and mesoporous silica nanoparticles with a silver nanoshell coat (CS-AgMSNs). The physicochemical properties of CS-AgMSNs films were characterized using various techniques. Further, the mechanical properties of CS-AgMSNs were evaluated and compared with those of undoped CS film. Moreover, the antimicrobial activities of CS-AgMSNs (with different concentrations) were assessed against E-coli, S. aureus, C. albicans, and A. niger. Our results demonstrated that increasing the concentrations of doped AgMSNs (10 to 40 mg) in CS films lowered their transparency and blocked light transmission effectively. The measured elastic modulus of CS-AgMSNs films (20 and 30 mg) showed a decrease in the stiffness of CS films. Also, the elongation at break for CS-AgMSNs (40 mg) indicated a better flexibility. CS-AgMSNs films (10-40 mg) showed an enhanced antimicrobial activity in a concentration-dependent manner compared to undoped CS films. Collectively, the results suggest that our nano-hybrid CS-AgMSNs matrix has unique and promising properties, and holds potential for use in the biomedical field, food packaging, and textile industry.
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Antiinfecciosos/farmacología , Fenómenos Químicos , Quitosano/farmacología , Nanocáscaras/química , Plata/química , Bacterias/efectos de los fármacos , Módulo de Elasticidad , Pruebas de Sensibilidad Microbiana , Nanocáscaras/ultraestructura , Fenómenos Ópticos , Porosidad , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Resistencia a la Tracción , Difracción de Rayos X , Levaduras/efectos de los fármacosAsunto(s)
Antiinfecciosos/farmacología , Derivados del Benceno/farmacología , Complejos de Coordinación/química , ADN/química , Hierro/química , Níquel/química , Triazoles/farmacología , Antiinfecciosos/química , Bacterias/efectos de los fármacos , Derivados del Benceno/química , Cationes , Complejos de Coordinación/farmacología , Estructura Molecular , Triazoles/química , Levaduras/efectos de los fármacosRESUMEN
Herein, tannic acid (TA)-reinforced chitosan (CHS)/ß-cyclodextrin (ß-CD) biocomposite membranes were prepared by TA solution incubating treatment. The functional groups, crystal structure, and morphological characterizations of the prepared biocomposite membranes were investigated using various methods. The biocomposite membranes were investigated in terms of their wettability, porosity, swelling degree, and water uptake. In vitro antioxidant investigation was carried out through DPPH assay. Moreover, the prepared biocomposite membranes were evaluated for their antimicrobial ability against three different microbial species. The introduction of TA effectively improved the swelling behavior, mechanical strength, and porosity of the biocomposite membranes. TA increased the tensile strength from 0.7 ± 0.2 MPa to a maximum of 2.2 ± 0.6 MPa and elongation at break from 26.9 ± 0.7% to a maximum of 36.7 ± 3.5%. The biocomposite membranes showed an initial burst release of TA (~40%) within 6 h, followed by a gradual release of 100% by 18 h. Furthermore, the introduction of TA into the biocomposite membranes further improved the antimicrobial activities against both bacteria and yeast, as well as the in vitro antioxidant potential. As a consequence, the prepared biocomposite membranes could potentially be used as scaffold in broaden biomedical fields due to their adaptable structure, porosity, greatly antioxidant, and antimicrobial activity.
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Antibacterianos/farmacología , Antioxidantes/farmacología , Materiales Biocompatibles/química , Quitosano/química , Fenómenos Mecánicos , Membranas Artificiales , Taninos/química , beta-Ciclodextrinas/química , Bacterias/efectos de los fármacos , Cinética , Pruebas de Sensibilidad Microbiana , Porosidad , Espectroscopía Infrarroja por Transformada de Fourier , Agua , Difracción de Rayos X , Levaduras/efectos de los fármacosRESUMEN
Chitosan (Ch) was reacted with seven benzaldehyde analogs separately through reductive amination in which the corresponding imines were formed and followed by reduction to produce N-(benzyl) chitosan (NBCh) derivatives. 1H NMR spectroscopy was used to characterize the products. The nanoparticles (NPs) of Ch and NBCh derivatives were prepared according to the ionotropic gelation mechanism between Ch products and sodium tripolyphosphate, followed by high-energy ultrasonication. Scanning electron microscopy, particle size, polydispersity index, and zeta potential were applied for the NPs examination. The particle size was ranged from 235.17 to 686.90 nm and narrow size distribution (PDI <1). The zeta potential of NPs was varied between -1.26 and -27.50 mV. The antimicrobial activity was evaluated against bacteria (Erwinia carotovora subsp. atroseptica, Erwinia carotovora subsp. carotovora, and Ralstonia solanacearum), fungi (Aspergillus flavus and Aspergillus niger), and yeast (Candida albicans). The action of NBCh derivatives was significantly higher than Ch. The NPs had considerably higher than the Ch and NBCh derivatives. The activity was directly proportional to the chemical derivatization of Ch and the zeta potential of the NPs. The antimicrobial efficacy of these derivatives formulated in a greener approach could become an alternative to using traditional antimicrobial applications in an environmentally friendly manner.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Quitosano/farmacología , Hongos/efectos de los fármacos , Nanopartículas , Antibacterianos/síntesis química , Antifúngicos/síntesis química , Bacterias/crecimiento & desarrollo , Quitosano/análogos & derivados , Quitosano/síntesis química , Hongos/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Levaduras/efectos de los fármacos , Levaduras/crecimiento & desarrolloRESUMEN
Indole-3-acetic acid (IAA) is the most common plant hormone of the auxin class and regulates various plant growth processes. The present study investigated IAA production by the basidiomycetous yeast Rhodosporidiobolus fluvialis DMKU-CP293 using the one-factor-at-a-time (OFAT) method and response surface methodology (RSM). IAA production was optimized in shake-flask culture using a cost-effective medium containing 4.5% crude glycerol, 2% CSL and 0.55% feed-grade L-tryptophan. The optimized medium resulted in a 3.3-fold improvement in IAA production and a 3.6-fold reduction in cost compared with those obtained with a non-optimized medium. Production was then scaled up to a 15-L bioreactor and to a pilot-scale (100-L) bioreactor based on the constant impeller tip speed (Vtip) strategy. By doing so, IAA was successfully produced at a concentration of 3569.32 mg/L at the pilot scale. To the best of our knowledge, this is the first report of pilot-scale IAA production by microorganisms. In addition, we evaluated the effect of crude IAA on weed growth. The results showed that weed (Cyperus rotundus L.) growth could be inhibited by 50 mg/L of crude IAA. IAA therefore has the potential to be developed as a herbicidal bioproduct to replace the chemical herbicides that have been banned in various countries, including Thailand.