Search Results (486)

Candida albicans and Staphylococcus aureus are opportunistic pathogens that cause life-threatening infections. This study focused on using photodynamic inactivation (PDI) to eliminate mixed biofilms of C. albicans–S. aureus formed on poly (urethane) (PU) discs functionalized with a nanocomposite layer containing phloxine B (PhB). Additionally, the effect of PDI on the ALS3 and HWP1 genes of C. albicans was examined in mixed biofilms. Spectral analysis showed a continuous release of PhB from the nanocomposite in Mueller–Hinton broth within 48 h, with a released amount of PhB < 5% of the total amount. The anti-biofilm effectiveness of the light-activated nanocomposite with PhB showed a reduction in the survival rate of biofilm cells to 0.35% and 31.79% for S. aureus and C. albicans, respectively, compared to the control biofilm on PU alone. Scanning electron microscopy images showed that the nanocomposite effectively reduced the colonization and growth of the mixed biofilm. While PDI reduced the regulation of the ALS3 gene, the HWP1 gene was upregulated. Nevertheless, the cell survival of the C. albicans–S. aureus biofilm was significantly reduced, showing great potential for the elimination of mixed biofilms. Full article

Background/Objectives: Actinobacteria are one of the largest bacterial phyla. These microbes produce bioactive compounds, such as antifungals, antibiotics, immunological modulators, and anti-tumor agents. Studies on actinobacteria isolated from the Brazilian Savannah biome (Cerrado) are scarce and mostly address metagenomics or the search for hydrolytic enzyme-producing microbes. Solanum lycocarpum (lobeira) is a tree widely employed in regional gastronomy and pharmacopeia in Central Brazil. Methods: In this work, 60 actinobacteria isolates were purified from the rhizosphere of S. lycocarpum. Eight Streptomyces spp. isolates were selected for in vitro antifungal activity against Cryptococcus neoformans H99, the C. neoformans 89-610 fluconazole-tolerant strain, C. gattii NIH198, Candida albicans, C. glabrata, and C. parapsilosis. The ability of the aqueous extracts of the isolates to induce the in vitro secretion of tumor necrosis factor (TNF-α), nitric oxide (NO), interleukin-6 (IL-6), and IL-10 by murine macrophages was also evaluated. Results: All extracts showed antifungal activity against at least two yeast species. Streptomyces spp. LAP11, LDB2, and LDB17 inhibited C. neoformans growth by 40–93%. Most extracts (except LAP2) also inhibited C. gattii. None inhibited C. albicans, but all inhibited C. glabrata (40–90%). Streptomyces sp. LAP8 extract increased nitric oxide production by approximately 347-fold in murine macrophages, while LDB11 extract suppressed LPS-induced TNF-α production by 70% and simultaneously increased IL-10 secretion, suggesting immunosuppressive potential. Conclusions: The results revealed that Cerrado actinobacteria-derived aqueous extracts are potential sources of antifungal and immunomodulatory biocompounds. Full article

The most prevalent growth of Candida cells is based on biofilm development, which causes the intensification of antifungal resistance against a large range of chemicals. Nanoparticles can be synthesized using green methods via various biological extracts and reducing agents to control Candida biofilms. This study aims to compare copper oxide nanoparticles (CuONPs) synthesized through chemical methods and those synthesized using Cinnamomum verum-based green methods against Candida infections and their biofilms isolated from Iraqi patients, with the potential to improve treatment outcomes. The physical and chemical properties of these nanoparticles were characterized using Fourier-transform infrared spectroscopy (FT-IR,) scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). Four strains of Candida were isolated and characterized from Iraqi patients in Tikrit Hospital and selected based on their ability to form biofilm on polystyrene microplates. The activity of green-synthesized CuONPs using cinnamon extract was compared with both undoped and doped (Fe, Sn) chemically synthesized CuONPs. Four pathogenic Candida strains (Candida glabrata, Candida lusitaniae, Candida albicans, and Candida tropicalis) were isolated from Iraqi patients, demonstrating high biofilm formation capabilities. Chemically and green-synthesized CuONPs from Cinnamomum verum showed comparable significant antiplanktonic and antibiofilm activities against all strains. Doped CuONPs with iron or tin demonstrated lower minimum inhibitory concentration (MIC) values, indicating stronger antibacterial activity, but exhibited weaker anti-adhesive properties compared to other nanoparticles. The antiadhesive activity revealed that C. albicans strain seems to produce the most resistant biofilms while C. glabrata strain seems to be more resistant towards the doped CuONPs. Moreover, C. tropicalis was the most sensitive to all the CuONPs. Remarkably, at a concentration of 100 µg/mL, all CuONPs were effective in eradicating preformed biofilms by 47–66%. The findings suggest that CuONPs could be effective in controlling biofilm formation by Candida species resistant to treatment in healthcare settings. Full article

Background/Objectives: The growing demand for biocompatible and fluoride-free alternatives in oral care has led to the development of formulations containing nano-hydroxyapatite (nanoHAP). This study aimed to evaluate the antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties of a novel mouthwash containing nanoHAP, zinc lactate, D-panthenol, licorice extract, and cetylpyridinium chloride, with particular focus on its efficacy against Staphylococcus aureus and its biofilm on various dental materials. Methods: The antimicrobial activities of the mouthwash KWT0000 and control product ELM were assessed via minimal inhibitory concentration (MIC) testing against selected Gram-positive and Gram-negative bacteria and Candida fungi. Antibiofilm activity was evaluated using fluorescence and digital microscopy following 1-h exposure to biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The efficacy was compared across multiple dental materials, including titanium, zirconia, and PMMA. Antioxidant capacity was determined using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay, and anti-inflammatory potential via hyaluronidase inhibition. Results: KWT0000 exhibited strong antimicrobial activity against S. aureus and C. albicans (MICs: 0.2–1.6%) and moderate activity against Gram-negative strains. Fluorescence imaging revealed significant biofilm disruption and bacterial death after 1 h. On metallic surfaces, especially polished titanium and zirconia, KWT0000 reduced S. aureus biofilm density considerably. The formulation also demonstrated superior antioxidant (55.33 ± 3.34%) and anti-inflammatory (23.33 ± 3.67%) activity compared to a fluoride-based comparator. Conclusions: The tested nanoHAP-based mouthwash shows promising potential in antimicrobial and antibiofilm oral care, particularly for patients with dental implants. Its multifunctional effects may support not only plaque control but also soft tissue health. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against Candida species. We evaluated the responses of nine reference species of Candida spp. and one hundred clinical isolates of C. albicans to 5-FUrd using the broth microdilution method. Additionally, we assessed the effect of 5-FUrd on selected virulence factors, including biofilm formation, cell adhesion, dimorphism, hydrolase secretion, and hemolytic activity, in the two most sensitive Candida species, C. albicans and C. parapsilosis. The frequency of spontaneous mutations occurring in these two Candida species under the influence of 5-FUrd was also determined. Finally, we examined the cytotoxic properties of 5-FUrd against human erythrocytes and zebrafish embryos. Our results demonstrated that 5-FUrd exhibits antifungal activity in vitro, inhibits biofilm formation, suppresses hyphal growth, reduces cell surface hydrophobicity, eradicates mature biofilms, and decreases the secretion of extracellular proteinases and hemolytic activity in C. albicans and C. parapsilosis cells. The overall mutation frequency under the selective pressure of 5-FUrd ranged from 2 × 10⁻⁵ to 1.2 × 10⁻⁴ per species. Notably, the exposure to 5-FUrd did not induce significant toxic effects on human erythrocytes or zebrafish embryos. This study highlights the potential clinical application of 5-FUrd as an anti-Candida agent. Full article

Background/Objectives: Agave amica (Medik.) Thiede & Govaerts (Asparagaceae family) is an ornamental bulbous species, widely used for its fragrance but less studied as a medicinal species. This study is aimed at assessing the phenolic profile and selected biological properties of ethanolic extracts obtained from the aerial parts and bulbs of A. amica cultivated in Romania. Methods: The phenolic composition was characterized by spectrophotometric methods and LC/MS analysis. The antioxidant activity was evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) and FRAP (Ferric reducing antioxidant power) tests, while the in vitro antimicrobial capacity was investigated by the agar-well diffusion, the broth microdilution, and the antibiofilm assays. Cytotoxicity was tested on a colorectal adenocarcinoma cell line (DLD-1) by a CCK-8 assay. Results: Both ethanolic extracts showed important polyphenol content and caffeic acid as their main compound. Significantly higher amounts of total polyphenols (44.25 ± 1.08 mg/g), tannins (12.55 ± 0.34 mg/g), flavonoids (9.20 ± 0.19 mg/g), caffeic acid derivatives (19.95 ± 0.05 mg/g), and also antioxidant activity (IC₅₀ = 0.82 ± 0.02 mg/mL, and 79.75 ± 1.80 µM TE/g, respectively) were found for the aerial parts extract compared to the bulbs one (p < 0.001). Notable anti-Candida albicans activity and moderate efficacy against Listeria monocytogenes and Staphylococcus aureus were displayed by both extracts against planktonic cells and biofilm. A dose-dependent cytotoxicity towards the colorectal adenocarcinoma cell line was recorded as well. Conclusions: This study brings novelty to the scientific literature by characterizing the phenolic profile and in vitro antimicrobial, antibiofilm, antioxidant, and antiproliferative activities of the ethanolic extracts obtained from A. amica, thus highlighting this herbal species’s medicinal potential. Full article

Solid-state microbial fermentation (SSMF) has been established as an effective bioprocessing strategy to augment the nutritional value of plant-derived feed substrates while reducing anti-nutritional factors (ANFs). However, there have been limited studies on the effects of microbial solid-state fermentation on the nutritional value and potential functional components in cottonseed hulls. This study investigated the nutritional enhancement of cottonseed hulls through anaerobic solid-state fermentation mediated by Candida utilis CU-3, while exploring the functional potential of the fermented feed by analyzing fungal community dynamics and metabolite profiling. The laboratory-preserved free gossypol-degrading strain Candida utilis CU-3 was inoculated into unsterilized, crushed, and screened cottonseed hulls for solid-state fermentation at room temperature for 10 days. The results demonstrated that, compared to the control group, the experimental group achieved a 61.90% increase in free gossypol degradation rate, a 27.78% improvement in crude protein content, and a 5.07% reduction in crude fiber, while crude fat showed no significant difference. During the fermentation process, microbial diversity decreased, and Candida utilis CU-3 became the dominant species. Untargeted metabolomics data revealed that cottonseed hulls inoculated with Candida utilis CU-3 produced functional bioactive compounds during fermentation, including chrysin, myricetin (anti-inflammatory, antibacterial, and antioxidant activities), and ginsenoside Rh2 (anticancer, antibacterial, and neuroprotective properties). This study demonstrates that inoculating Candida utilis CU-3 into cottonseed hulls enhances their health-promoting potential through the biosynthesis of diverse functional metabolites, providing a theoretical foundation for improving the nutritional profile of cottonseed hull-fermented feed. Full article

Plantago ovata has been utilized as an effective natural remedy with minimal side effects, offering a promising alternative to synthetic pharmaceuticals. The supercritical fluid extraction (SFE) of Plantago ovata leaves yielded 0.417 g and 0.532 g at 40 °C and 80 °C, respectively. The 40 °C extract exhibited stronger antimicrobial activity, with minimum inhibitory concentrations (MICs) as low as 15.62 µg/mL and minimum bactericidal concentrations (MBCs) as low as 31.25 µg/mL against Bacillus subtilis and Candida albicans. In contrast, the 80 °C extract demonstrated reduced activity, with MICs and MBCs up to 250 and 500 µg/mL, respectively. The 40 °C extract also showed superior lipase inhibition (IC₅₀ = 17.21 µg/mL) compared to the 80 °C extract (IC₅₀ = 26.42 µg/mL), although orlistat remained the most potent (IC₅₀ = 6.02 µg/mL). In addition, cytotoxicity assays revealed stronger effects of the 40 °C extract on Caco-2 colon cancer cells (IC₅₀ = 109.47 µg/mL) compared to the 80 °C extract (IC₅₀ = 174.81 µg/mL). These results suggest that the lower-temperature SFE of P. ovata yields extracts with enhanced antimicrobial, anti-obesity, and anticancer activities, supporting its potential for pharmaceutical and nutraceutical applications. Full article

Background/Objectives: Candidiasis, an opportunistic fungal infection caused by Candida species, is a major health problem, particularly in immunocompromised individuals. Increasing resistance of yeasts such as Candida spp. to pharmacological antifungal agents makes it necessary to explore alternative treatments. The aim of this study was to evaluate the antifungal potential of Gomortega keule essential oil (GKEO) against Candida spp. by assessing growth and development at 24 and 48 h. Encapsulation and characterization of a stable nanoemulsion were carried out to enhance efficacy. Methods: The anti-yeast activity of both free GKEO and the nanoemulsion against Candida albicans, C. glabrata, and C. guilliermondii was evaluated using a microdilution method to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 24 and 48 h. Results: GC-MS/MS analysis identified forty-one components in GKEO, the main ones being eucalyptol (21.41%), 4-terpineol (19.62%), and α-terpinyl acetate (13.89%). Antifungal assays revealed that both free and nanoemulsion-formulated GKEO inhibited the growth of all tested Candida strains. At 48 h, the nanoformulated GKEO achieved a MIC value of 32 µg/mL and an MFC of 64 µg/mL for C. albicans and C. glabrata and showed higher antifungal activity compared to the free oil, in particular against C. albicans, exhibiting a four-fold lower MFC value. The activity of the nanoformulation was comparable to or better than fluconazole against C. glabrata and C. guilliermondii. Conclusions: The GKEO nanoemulsion potentiated anti-yeast activity against Candida spp. The formulation improved the efficacy of GKEO, suggesting its potential as an alternative or adjunctive treatment for candidiasis. Full article

This article investigates the antifungal activity of clove essential oil (CEO) against Candida albicans, as well as its inhibitory effects on C. albicans biofilm formation and the associated developmental processes. Furthermore, it evaluates the therapeutic efficacy of CEO in a mouse model of intestinal C. albicans infection and explores its impact on intestinal microbiota. Additionally, 16S rRNA high-throughput sequencing was conducted to analyze the alterations in the intestinal microbiota. The findings indicate that the administration of CEO in mice infected with C. albicans resulted in a normalization of body weight and an improvement in their symptoms. Histological analysis utilizing HE and PAS staining demonstrated that CEO exerted beneficial effects on the intestinal mucosal status of these infected mice. Furthermore, ELISA results revealed a dose-dependent reduction in the levels of IL-6, IL-8, and IL-17A within the small intestinal tissues of C. albicans-infected mice. Additionally, 16S rRNA gene analysis indicated that CEO effectively enhanced the richness and diversity within the intestinal microbiota of CEO treatment groups of mice that were investigated. Overall, CEO exhibits therapeutic potential against inflammation induced by intestinal C. albicans infection in mice. This effect can be attributed to its anti-inflammatory properties as well as its capacity to regulate the composition of intestinal flora. Full article

Human pathogenic fungi are the source of various illnesses, including invasive, cutaneous, and mucosal infections. One promising solution is using nanoparticles (NPs) as an antifungal agent. The current study aims to assess the antimicrobial and antifungal effects of drug-loaded silver nanoparticles (AgNPs) with previously reported mebeverine analogue (MA) as a potential drug candidate targeting gut microbiota and inflammation in the gastrointestinal tract. Density Functional Theory (DFT) calculations were conducted to identify possible mechanisms by which AgNPs could prevent microorganisms from growing. In vitro and ex vivo anti-inflammatory, in vitro antimicrobial, ex vivo spasmolytic activities, and in vitro hepatic cell morphology and proliferation of drug-loaded AgNPs were assessed. The drug-loaded AgNPs were considered to have promising antifungal activity against all tested fungal strains, Aspergillus niger, Penicillium chrysogenum, and Fusarium moniliforme, and yeasts, Candida albicans, Saccharomyces cerevisiae, and good antimicrobial activity against Gram-positive and Gram-negative bacterial strains. The results of in vitro and ex vivo determination of anti-inflammatory activity indicated that the drug-loaded AgNPs preserved MA’s anti-inflammatory activity and decreased inflammation. A similar effect was observed in spasmolytic activity measurements. Drug-loaded AgNPs also influenced the morphology and proliferation of hepatic cells, indicating a potential for improved gut and liver therapeutic efficacy. Each test was performed in triplicate, and the results were reported as mean values. Based on the results, drug-loaded AgNPs might be a promising antimicrobial agent, maintaining the MA’s potential as a spasmolytic and anti-inflammatory agent. Future in vivo and preclinical experiments will contribute to establishing the in vivo properties of drug-loaded AgNPs. Full article

The pathogenicity of Candida spp. poses a persistent challenge, particularly in hospital environments where these species proliferate and cause opportunistic infections. Many strains have developed resistance to commonly used antifungal agents, including azoles, polyenes, and echinocandins, complicating treatment, especially in immuno-compromised patients. Understanding the mechanisms underlying antifungal resistance, such as mutations in genes involved in ergosterol biosynthesis, efflux pump activity, and enzymatic pathways, is crucial for developing targeted interventions. Given the challenges associated with discovering new antifungal agents, medicinal plants have emerged as a promising source of bioactive compounds with anti-Candida activity. Secondary metabolites, including terpenoids, alkaloids, flavonoids, and tannins, exhibit various mechanisms of action, such as biofilm inhibition, membrane disruption, and oxidative stress induction. However, challenges such as extract standardization, and the lack of clinical studies continue to limit their therapeutic application. This review underscores the potential of medicinal plants as complementary or alternative strategies to conventional antifungal therapies, emphasizing the need for multidisciplinary research to overcome these hurdles and harness the therapeutic potential of natural products. Full article

Objective: This study aimed to develop and characterize the physicochemical properties of a self-emulsion drug delivery system (SNEDDS) incorporating galangal extract (GE) and lemongrass oil (LGO). Then, to develop mouthwash powders containing GE- and LGO-loaded SNEDDS (GL-mouthwash powder) as a promising alternative for preventing and treating denture stomatitis. Methods: The solubility of GE in various vehicles was determined. Subsequently, pseudo-ternary phase diagrams of the different ingredients, oil (LGO), surfactant (Tween^® 80), and co-surfactant (Propylene glycol) were selected to develop the SNEDDS. Then, SNEDDS containing GE and LGO (GL-SNEDDS) were prepared and characterized. The optimized liquid GL-SNEDDS was transformed into GL-mouthwash powder by absorbing onto mannitol and blending with a sweetener. Subsequently, various evaluations including drug recovery, moisture content, emulsification time, stability, anti-Candida activity, and in vitro cytotoxicity were performed. Results: The developed SNEDDS formulation improved GE and LGO solubility. The optimized GL-SNEDDS exhibited a small droplet size of 148.2 ± 2.1 nm with a polydispersity index of 0.11 ± 0.03 and a zeta potential of 2.14 ± 0.11 mV. In addition, the GL-mouthwash powder demonstrated a high drug recovery of >80% with a low moisture of <10% and exhibited greater physicochemical stability under accelerated conditions. The developed GL-mouthwash powder rapidly formed a stable nanoemulsion within 2 min after reconstitution. Interestingly, GL-mouthwash powder exhibited strong anti-Candida activity with no toxicity to human fibroblast cells, which demonstrated superior biocompatibility relative to existing commercial products. Conclusions: These findings suggest that GL-mouthwash powder has potential as an alternative prevention and treatment of oral Candida infection. Full article

In recent years, the incidence of acute and chronic inflammatory diseases has increased significantly worldwide, intensifying the search for new therapeutic agents, especially anti-inflammatory drugs. Therefore, the aim of this work was to synthesize, biologically assess, and explore the structure–activity relationships of new compounds containing the cyclohex-1-ene-1-carboxylic acid moiety. Six new derivatives, 2a–2f, were synthesized through the reaction of amidrazones 1a–1f with 3,4,5,6-tetrahydrophthalic anhydride. Their toxicity was evaluated in cultures of human peripheral blood mononuclear cells (PBMCs). Additionally, their antiproliferative properties and effects on the synthesis of TNF-α, IL-6, IL-10, and IL-1β were assessed in mitogen-stimulated PBMCs. The antimicrobial activity of derivatives 2a–2f was determined by measuring the minimal inhibitory concentration (MIC) values against five bacterial strains—Staphylococcus aureus, Mycobacterium smegmatis, Escherichia coli, Yersinia enterocolitica, and Klebsiella pneumoniae—and the fungal strain Candida albicans. All compounds demonstrated antiproliferative activity, with derivatives 2a, 2d, and 2f at a concentration of 100 µg/mL being more effective than ibuprofen. Compound 2f strongly inhibited the secretion of TNF-α by approximately 66–81% at all studied doses (10, 50, and 100 µg/mL). Derivative 2b significantly reduced the release of cytokines, including TNF-α, IL-6, and IL-10, at a high dose (by approximately 92–99%). Compound 2c exhibited bacteriostatic activity against S. aureus and M. smegmatis, while derivative 2b selectively inhibited the growth of Y. enterocolitica (MIC = 64 µg/mL). Some structure–activity relationships were established for the studied compounds. Full article