Search Results (855)

Lactoferrin (Lf) occurs predominantly within milk, coexisting with measurable levels across different glandular products and body fluids. Lf exhibits variation in relative molecular mass, influenced by its biological source and glycosylation profile; nevertheless, it is a close to 80 kDa glycoprotein. Provided that its bioactive structure is preserved, Lf performs a spectrum of physiological roles, comprising antioxidant, antifungal, antiviral, antiapoptotic, and antimicrobial actions. To sustain its bioactivity after isolation and ensure its effectiveness in subsequent applications, optimal conditions must be established throughout the optimization protocol, since inadequate optimization of parameters such as pH, temperature, ion balance, and protease activity may lead to aggregation, denaturation, and deterioration in functional regions, including the iron-binding domains. This review offers a comprehensive framework that associates isolation methodologies with structural integrity, preservation of iron-binding domains, and antimicrobial performance. Ion-exchange, affinity-based, and membrane-based approaches are systematically evaluated from analytical and functional perspectives, thereby yielding a synthesis that facilitates procedure selection and optimization for Lf isolation. In addition, the objectives of analytical characterization techniques implemented following isolation and the broadening scope of biotechnological applications of Lf are outlined. Full article

Imidazole is, from a structural point of view, a heterocycle consisting of three C atoms and two N atoms, belonging to the class of diazoles, having two N atoms at the first and third positions in the aromatic ring. Being a polar and ionizable aromatic compound, it has the role of improving the pharmacological properties of lead molecules, thus being used to optimize their solubility and bioavailability. Imidazole is a constituent of many important biological compounds, like histidine, histamine, and purine compounds, the most widespread heterocyclic compound in nature. In current practice, substituted imidazole derivatives play a major role in antifungal, antibacterial, anti-inflammatory, CNS active compounds, antiprotozoal, as well as anticancer therapy. Thus, imidazole derivatives have demonstrated significant anticancer activities by inhibiting the key metabolic pathways essential for tumor cell growth and survival. Nitroimidazoles, for instance, have been employed as hypoxia-directed therapeutic agents, targeting oxygen-deprived tumor tissues, while mercaptopurine derivatives are well-established in oncological treatments. Structural modifications of the imidazole nucleus have led to the novel compounds exhibiting increased selective cytotoxicity against cancer cells, while sparing normal healthy cells. In accordance with what has been stated, this review highlights recent research on the medicinal and pharmaceutical interest of novel imidazole derivatives, emphasizing their potential in the development of new drugs. Full article

The growing prevalence of multidrug-resistant (MDR) Candida spp. necessitates the development of new antifungal strategies. Photodynamic therapy (PDT), already widely used in the treatment of various oral infections, is based on the synergistic interaction of three key elements: a photosensitizer capable of selectively binding to microbial cells, a light source with the appropriate wavelength, and the presence of molecular oxygen. This interaction results in the production of singlet oxygen and reactive oxygen species, responsible for the selective destruction of microorganisms. In recent years, numerous natural compounds have been explored as potential photosensitizers. Olive oil, a cornerstone of the Mediterranean diet, was recently recognized by the U.S. Food and Drug Administration as a medicinal substance thanks to its soothing, immunomodulatory, and antimicrobial properties, which have also been documented in regard to oral administration. Materials and Methods: The aim of this in vitro study was to evaluate the efficacy of activated olive oil as a novel photosensitizer in PDT against Candida species. Oral MDR clinical isolates of C. albicans, C. krusei, and C. glabrata were analyzed using the Kirby–Bauer method according to EUCAST protocols. Six different experimental conditions were considered for each strain: (i) 100 μL of extra-virgin olive oil (EVOO); (ii) 100 μL of EVOO pre-activated with 3% H₂O₂ (EVOO-H); (iii) 100 μL of EVOO irradiated for 5 min with polarized light (480–3400 nm, 25 W); (iv) 100 μL of EVOO-H subjected to the same polarized light; (v) 100 μL of EVOO irradiated for 5 min with a 660 nm diode laser (100 mW); and (vi) 100 μL of EVOO-H irradiated with the same laser. All plates were incubated at 37 °C for 48 h. Results: The results showed a variable response among the different Candida species. C. glabrata showed sensitivity to all experimental conditions, with a 50% increase in the diameter of the inhibition zone in the presence of polarized light. C. krusei showed no sensitivity under any of the conditions tested. C. albicans showed antifungal activity exclusively when EVOO-H was activated by light. In particular, activation of EVOO and EVOO-H with polarized light resulted in the largest inhibition zones. Conclusions: In conclusion, olive oil, both alone and pre-activated with hydrogen peroxide, can be considered an effective photosensitizer against drug-resistant Candida spp., especially when combined with polarized light. Full article

The global food industry is undergoing a major shift driven by increasing consumer demand for clean-label and naturally preserved foods. Fresh pasta is highly vulnerable to fungal damage because of its high water activity (a_w > 0.85), typically ranging between 0.92 and 0.97, moderate to near-neutral pH (around 5.0–7.0), and nutrient-rich composition, all of which create favorable conditions for fungal growth during refrigeration, mainly by genera such as Penicillium and Aspergillus. Fungal contamination results in significant economic losses due to reduced product quality and poses potential health risks associated with mycotoxin production. Although conventional chemical preservatives are relatively effective in preventing spoilage, their use conflicts with clean-label trends and faces growing regulatory and consumer scrutiny. In this context, antifungal lactic acid bacteria (LAB) have emerged as a promising natural alternative for biopreservation. Several LAB strains, particularly those isolated from cereal-based environments (e.g., Lactobacillus plantarum and L. amylovorus), produce a broad spectrum of antifungal metabolites, including organic acids, phenylalanine-derived acids, cyclic dipeptides, and volatile compounds. These metabolites act synergistically to inhibit fungal growth through multiple mechanisms, such as cytoplasmic acidification, energy depletion, and membrane disruption. However, the application of LAB in fresh pasta production requires overcoming several challenges, including the scale-up from laboratory to industrial processes, the maintenance of metabolic activity within the complex pasta matrix, and the preservation of desirable sensory attributes. Furthermore, regulatory approval (GRAS/QPS status), economic feasibility, and effective consumer communication are crucial for successful commercial implementation. This review analyzes studies published over the past decade on fresh pasta spoilage and the antifungal activity of lactic acid bacteria (LAB), highlighting the progressive refinement of LAB-based biopreservation strategies. The literature demonstrates a transition from early descriptive studies to recent research focused on strain-specific mechanisms and technological integration. Overall, LAB-mediated biopreservation emerges as a sustainable, clean-label approach for extending the shelf life and safety of fresh pasta, with future developments relying on targeted strain selection and synergistic preservation strategies. Full article

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC₅₀ values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC₅₀ of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5–1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens. Full article

Aspergillus fumigatus, a saprophytic fungus, causes aspergillosis, primarily affecting the immunocompromised. The efficacy of triazole antifungals is compromised by resistance that has developed both clinically and environmentally. Widespread agricultural use of similar triazole fungicides selects for resistant genotypes, leading to potential food contamination and compromising treatment. This study assessed the presence of azole-resistant A. fumigatus in minimally processed food items commonly consumed in Brazil. A total of 25 commercial samples, including black pepper, yerba mate, and green coffee beans, were collected from different regions. Forty-two A. fumigatus isolates were recovered and screened for susceptibility to agricultural and clinical triazoles by determining EC₅₀ values for tebuconazole (0.04–0.7 µg/mL), itraconazole (0.06–0.5 µg/mL), and voriconazole (0.07–0.15 µg/mL). Sequence analysis of the CYP51A gene revealed the presence of M172V mutation, none of which are associated with resistance. Microsatellite genotyping indicated high genotypic diversity and genetic relatedness among isolates from different food sources. Although no azole-resistant phenotypes were identified, the consistent recovery of A. fumigatus from products not directly exposed to azole fungicides highlights the need for continued surveillance. Agricultural environments remain critical hotspots for the emergence and dissemination of resistance, reinforcing the importance of integrated One Health strategies in antifungal resistance monitoring. Full article

Two series of tri(2-furyl)- and triphenylphosphine-gold(I) complexes, with pyridyl- and pyrimidine-thiolate ligands containing electron-donating (-CH₃) and electron-withdrawing (-CF₃) substituents were synthesized and investigated for cell viability inhibitions. Prior results indicate that several of the gold(I) complexes in these series have high antifungal properties. The observed link between antifungal and anticancer activity provided motivation to investigate their antiproliferative effects, reported here. The synthesized compounds from both series were characterized by ¹H, ¹³C, and ³¹P NMR spectroscopy, mass spectrometry (MS), infrared and UV-Vis spectroscopy, and solution stability studies. In addition, an X-ray crystallographic study was conducted on one of the gold(I) complexes. Analyte solubilities in McCoy’s 5A cell media were evaluated by ICP-MS. Initial screening studies were conducted on the two series to evaluate cell viability using the SK-BR-3 cell line. All ten gold(I) complexes exhibited sub-µM cytotoxicity and the most potent representatives, one from each series, were selected for further evaluation in four additional cell lines. Half-maximal effective concentrations (EC₅₀) were determined for the MCF7 and MDA-MB-231 malignant mammary cell lines as well as the two control cell lines, HEK293T and MCF10A, to probe for specificity. Results indicate significant selectivity towards inhibition of cancer cells compared to non-transformed for tri(2-furyl)- and triphenylphosphine-gold(I) complexes with the 3,5-dimethylpyrimidine thiolate ligand when dissolved in cell media. Additional studies including 1% DMSO as a solubilizing agent revealed its significant impact on cellular responses. Full article

Background: Antifungal resistance among Candida species and related genera, coupled with the lack of new drugs, poses a significant threat to public health. Several studies have demonstrated a relationship between virulence factors and resistance. Current objectives include identifying new targets and searching for new natural molecules. Carvacrol, a natural phenolic compound, has been shown to have antimicrobial properties; however, its impact on the virulence of species other than Candida albicans and related yeast genera remains underexplored. Methods: The antifungal activity of carvacrol was evaluated against clinical isolates of Candidozyma auris, Meyerozyma guilliermondii, and Candida dubliniensis, as well as its effect on adhesion, hydrophobicity, biofilm formation and osmotic stress tolerance. In vivo activity was assessed using the Galleria mellonella infection model at MIC concentrations. Results: Carvacrol inhibited adherence and significantly reduced both early and preformed biofilms in M. guilliermondii and C. dubliniensis. In C. auris, the compound produced a modest reduction in biofilm activity but significantly enhanced larval survival in the in vivo model (~20%, p < 0.01). Carvacrol also induced increased tolerance of C. auris to osmotic stress, suggesting activation of adaptive pathways. Conclusions: Carvacrol exhibits species-specific effects, acting as an antivirulence modulator in M. guilliermondii and C. dubliniensis and attenuating virulence in vivo in C. auris. These findings support the potential of carvacrol as an adjuvant antifungal strategy, particularly against C. auris, and highlight the relevance of targeting virulence traits to reduce selective pressure and limit antifungal resistance. Full article

Fisheries bycatch, while representing a major ecological concern due to the incidental capture of non-target species, also constitutes an underexplored source of marine biomass with biotechnological potential. This study aimed to generate and characterize bioactive peptides from the muscle tissue of three common bycatch species from the Brazilian coast: Paralonchurus brasiliensis, Micropogonias furnieri, and Hepatus pudibundus. Muscle homogenates were hydrolyzed using either Alcalase or Protamex to produce peptide-rich hydrolysates, which were analyzed through SDS-PAGE, HPLC-UV, MALDI-TOF, and LC-MS/MS. De novo sequencing and bioinformatic analyses predicted bioactivities that were subsequently validated by in vitro assays. The results demonstrated that enzyme selection strongly influenced both peptide profiles and bioactivity. The Protamex hydrolysate of P. brasiliensis (PBP) exhibited potent antifungal activity, inhibiting Candida albicans growth by 81%, whereas the Alcalase hydrolysate (PBA) showed moderate inhibition of Staphylococcus aureus (29%). No significant effect was observed against Escherichia coli. Overall, this study highlights a sustainable strategy for the valorization of fisheries bycatch through the production of bioactive marine peptides and identifies P. brasiliensis hydrolyzed with Protamex as a promising source of anti-Candida peptides for pharmaceutical and nutraceutical applications. Full article

Invasive Candida infections in the neonatal intensive care unit (NICU) are associated with significant morbidity and mortality, particularly among extremely preterm neonates. Early treatment with antifungals is critical to improve survival rates and avoid long-term adverse outcomes. Prevention with antifungal prophylaxis in high-risk neonates has been shown to reduce the prevalence of invasive Candida infections effectively. However, the irrational and/or inappropriate use of antifungals has been documented. This narrative review aims to provide an overview of the rationales for the inappropriate use of antifungals in the NICU, the consequences that ensue, and the promising strategy of antifungal stewardship programs to optimize antifungal use. The nonspecific clinical presentation of systemic Candida infections and the lack of rapid, accurate diagnostic techniques for Candida identification and specification in most settings lead to a high rate of empirical treatment in neonates without a proven infection. Moreover, evidence on the optimal dosing of antifungal agents and the treatment duration in the neonatal population is lacking, which may result in excessive or subtherapeutic drug exposure. Antifungal misuse is associated with microbiological consequences, including the emergence of antifungal-resistant Candida strains, and clinical consequences, such as drug toxicities and alterations in the intestinal mycobiome. It is therefore imperative to optimize antifungal use in the NICU. The implementation of antifungal stewardship programs, which, through a multidisciplinary approach, aim to improve diagnosis and guide clinicians on antifungal selection, dosing, and duration for both prevention and treatment according to the local epidemiology, represents a promising strategy for antifungal optimization in the NICU. Full article

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1–5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC₅₀ = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models Full article

Contamination of agricultural products such as maize by fungi is a significant concern worldwide, as it can compromise food safety and quality. In recent years, the use of microorganisms as natural food preservatives has gained interest. Probiotic lactic acid bacteria (LAB) and their metabolites are considered a promising strategy to reduce fungal growth and limit other food contaminants. This study aimed to characterize, screen and compare the probiotic properties and antifungal activity of LAB of maize origin. A total of 23 LAB isolates obtained from untreated maize grains were identified through 16S rRNA gene sequencing as Weissella viridenscens (34.7%), Pediococcus pentosaceus (34.7%), Enterococcus durans (17.4%), Leuconostoc citreum (9%), and Enterococcus faecium (4.3%). All isolates demonstrated acid, phenol, and bile salt tolerance; surface hydrophobicity; and antagonistic activity against selected bacterial foodborne pathogens. Notably, Enterococcus sp. showed the strongest inhibitory activity against Escherichia coli ATCC 5211 (21 mm inhibition zone) and Staphylococcus aureus (17 mm inhibition zone), whereas Pediococcus sp. exhibited the highest antagonistic effect against Listeria monocytogenes (18.7 mm inhibition zone). Furthermore, E. durans and P. pentosaceus demonstrated the strongest antifungal activity, effectively inhibiting the growth of Alternaria tenuissima (F22FR) and Fusarium oxysporum (F44FR), respectively. Overall, all the LAB strains isolated from this study showed considerable potential for use in the food industry as probiotics, starter cultures for functional food fermentations, bio-preservatives and biocontrol agents against toxigenic fungi and pathogenic bacteria, with E. durans standing out for its exceptional performance. Future research will explore the ability of these isolates and/or their enzymes to degrade mycotoxins commonly found in maize, a staple food in many African countries. Full article

The open ocean cage aquaculture system is facing considerable challenges with disease outbreaks resulting from over-farming and the rise of resistance to antimicrobial treatment. However, the environmental consequences of antibiotic usage, including ecological contamination and the acceleration of antimicrobial resistance, underscore the urgent need for sustainable alternatives in aquaculture disease management. Lipopeptides, which are a compound that can be produced by marine bacteria such as Bacillus amyloliquefaciens or Bacillus subtilis, could represent a new solution. This review article comprehensively evaluates the feasibility of marine bacterial lipopeptides for sustainable disease management in open sea cage aquaculture. Lipopeptides, including surfactins, fengycins, iturins, and the clinically used daptomycin, have notable antiviral, antifungal, and antimicrobial properties, and can have positive effects on the immune system. Notably, lipopeptides have a remarkable antioxidant profile and excellent free radical scavenging ability, making them interesting candidates for improving disease resistance in fish relating to oxidative stress. The surfactins and iturins have amphiphilic structure and can destabilize pathogen cell membranes, inhibit biofilm formation and elicit host immune responses. This represents a paradigm shift in targeting multiple pathogens of aquaculture like Vibrio spp. and Aeromonas spp. Surfactins and iturins show broad-spectrum activity, while fengycins are selectively active against fungal threats. Daptomycin, which is primarily derived from Streptomyces, demonstrates the potential of the lipopeptide class to be developed therapeutically, which is something that tends to be overlooked. Unlike synthetic antibiotics, they are also biodegradable; therefore, there is much less environmental impact from lipopeptides. The complexity of the structure may have also some impact on the rate of development of resistance, if any. Their commercialization is possible; however, the main hurdles that need to be solved to improve aquaculture are the biologically scalable production, the economically viable purification, and the stability for practical application at sea. Integrating lipopeptides into disease management systems could also ensure the sustainability of open ocean cage aquaculture and reduce unnecessary antibiotic application. Full article

A novel series of benzoxazole-derived iminocoumarins was synthesized via a Knoevenagel condensation and fully characterized using NMR, UV–Vis spectroscopy, and computational methods. Their photophysical properties were systematically examined in solvents of varying polarity, revealing pronounced effects of both substituents and solvent environment on absorption maxima and intensity. Derivatives bearing electron-donating substituents on the coumarin core exhibited distinct and reversible pH-responsive spectral shifts, confirming their potential as optical pH probes. Experimental pK_a values derived from absorption titrations showed excellent agreement with DFT-calculated data, validating the proposed protonation-deprotonation equilibria and associated electronic structure changes. Structure–property relationships revealed that electron-donating groups enhance intramolecular charge transfer, while electron-withdrawing substituents modulate spectral response and stability. In parallel, the compounds were evaluated for antiproliferative, antiviral, and antifungal activities in vitro. Strong electron-donating substituents were associated with potent but non-selective cytotoxicity, whereas derivatives bearing electron-withdrawing groups displayed moderate and more selective antiproliferative effects against leukemia cell lines. Antifungal screening revealed moderate inhibition of phytopathogenic fungi, particularly for compounds with electron-withdrawing or methoxy substituents. Overall, these findings demonstrate that benzoxazole iminocoumarins represent a promising class of multifunctional heterocycles with potential applications as optical pH sensors and scaffolds for bioactive compound development. Full article

Background: This research aimed to investigate the antifungal and antibiofilm action of Lavandula angustifolia essential oil (LaEO) against certain Candida species and its toxicity on human keratinocytes. Methods: The minimum inhibitory concentration (MIC) and sessile minimum inhibitory concentration (SMIC) of LaEO were both determined by broth microdilution assays. The influence of LaEO treatment on the ultrastructural morphology of the biofilm and germ tubes was evaluated by scanning electron microscopy (SEM) and light microscopy. In vitro cytotoxicity studies were conducted using human HaCaT epidermal keratinocytes. Results: LaEO showed fungicidal action for all Candida species (125–4000 μg/mL). The SMIC_>90 (C. albicans) ranged between 10,000 and 20,000 μg/mL and resulted in quantitative and qualitative cellular changes. LaEO also inhibited the developmental germ tube kinetics of C. albicans. The 50% cytotoxic concentration (CI₅₀) for HaCaT cells was estimated at 420 μg/mL of LaEO, resulting in a selectivity index (SI) of 0.376 to 5.753 for planktonic cells and 0.056 to 0.321 for biofilm phases. Conclusions: LaEO was found to have antifungal action against Candida species and inhibited the pathogenic morphology of C. albicans. Its antibiofilm effects are comparable to the antifungal agent nystatin, and it can become an important component for the development of natural products applicable to alternative and complementary medicine and dentistry. Full article