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Background: Vulvovaginitis is common in women of reproductive age group characterized by purulent white discharge. The incidence of vulvovaginitis has risen recently due to the resistance of Candida species to commonly used antifungal agents and recurrent infections. Objective: The study aimed to determine the prevalence, associated factors, and antifungal susceptibility patterns of vaginal candidiasis among pregnant women attending Bule Hora University Teaching Hospital. Methods: A hospital-based cross-sectional study was conducted from May 2023 to August 2023. Using systematic random sampling, 317 pregnant women participated in the study. Sabouraud Dextrose Agar and Chromogenic Candida Differential Agar were used to isolate and identify Candida species from clinical samples. Antifungal susceptibility was performed using a modified disc diffusion method. Epi data version 4.6 was used for data entry and Statistical Packages for Social Sciences version 25 was used for statistical analysis. A P-value < 0.05 was declared statistically significant. Result: The prevalence of vaginal candidiasis was 26.8% (95%, CI 21.9–31.72%). History of using contraceptives (AOR = 5.03, 95%CI, 1.21–11.37), past vaginal candidiasis (AOR = 6, 95%CI, 1.61–12.92), pregnant women infected with human immunodeficiency virus (HIV) (AOR = 4.24, 95%CI, 1.23–14.14), diabetic mellitus (AOR = 2.17, 95%CI, 1.02–4.64), history of antibiotic use (AOR = 3.55, 95%CI, 1.67–12.75), pregnant women in third trimester (AOR = 8.72, 95%CI, 1.30–23.07), were the significantly associated factors for vaginal candidiasis. The study revealed that itraconazole, amphotericin B, and miconazole were the most effective antifungal drugs for all Candida isolates. Conclusion: The present study has identified a high prevalence of vaginal candidiasis among pregnant women. The isolated Candida species showed resistance to fluconazole, ketoconazole, and clotrimazole. Therefore, healthcare providers should increase awareness of the risks of Candida infections to reduce Candida species among pregnant women. Physicians should prescribe suitable medications based on antifungal drug test outcomes to treat pregnant women with vaginal candidiasis. [ABSTRACT FROM AUTHOR]

Antifungal resistance remains a significant public health threat, yet poorly investigated. This study for the first time investigated the antifungal profile of moulds isolated from groundwaters in a rural community of Osun State, Southwest Nigeria. Groundwater samples were collected during dry and rainy seasons, and processed for mould isolation using standard methods. The isolates were presumptively identified and screened for in vitro susceptibility using 4 antifungals conventionally employed in clinical cases. Multiple antifungal resistance phenotypes and indices were equally evaluated. Representative of each putatively identified species were confirmed using molecular techniques. A total of 29 and 27 moulds were obtained during the dry and rainy seasons, respectively. Genus Aspergillus was the most prevalent (30.4%). Of the 56 isolates subjected to antifungal susceptibility testing, 55(98%) were resistant to fluconazole, followed by flucytosine 49(88%), ketoconazole 45(80%) and amphotericin B 31(55%). Exactly 46 isolates were multidrug-resistant, 23(50%) each, to 3 and 4 drugs, respectively. The multiple antifungal resistance index (MARI) evaluated was 1 in all the samples A-Q, except C (0.75), transcending the threshold limit of 0.2, indicating the isolates to be of high antifungal usage origin. The molecularly identified species had 99–100% similarity with reference strains from GenBank and evolutionary relationship of taxa revealed 10 distinct clades. The outcome of this study reveals a rise in the frequency of antifungal resistance in moulds towards standard drugs, thus, advocating for adequate investigations targeted at monitoring antifungal resistance in groundwater milieus. [ABSTRACT FROM AUTHOR]

Fungi are ubiquitous in the environment and play a key role in the decomposition and recycling of nutrients. On the one hand, their special properties are a great asset for the agricultural and industrial sector, as they are used as source of nutrients, producers of enzymes, pigments, flavorings, and biocontrol agents, and in food processing, bio-remediation and plant growth promotion. On the other hand, they pose a serious challenge to our lives and the environment, as they are responsible for fungal infections in plants, animals and humans. Although host immunity opposes invading pathogens, certain factors favor the manifestation of fungal diseases. The prevalence of fungal infections is on the rise, and there is an alarming increase in the resistance of fungal pathogens to approved drugs. The limited number of antimycotics, the obstacles encountered in the development of new drugs due to the poor tolerability of antifungal agents in patients, the limited number of unique antifungal targets, and the low species specificity contribute to the gradual depletion of the antifungal pipeline and newly discovered antifungal drugs are rare. Promising candidates as nextgeneration therapeutics are antimicrobial proteins and peptides (AMPs) produced by numerous prokaryotic and eukaryotic organisms belonging to all kingdom classes. Importantly, filamentous fungi from the order Eurotiales have been shown to be a rich source of AMPs with specific antifungal activity. A growing number of published studies reflects the efforts made in the search for new antifungal proteins and peptides (AFPs), their efficacy, species specificity and applicability. In this review, we discuss important aspects related to fungi, their impact on our life and issues involved in treating fungal infections in plants, animals and humans. We specifically highlight the potential of AFPs from Eurotiales as promising alternative antifungal therapeutics. This article provides insight into the structural features, mode of action, and progress made toward their potential application in a clinical and agricultural setting. It also identifies the challenges that must be overcome in order to develop AFPs into therapeutics. [ABSTRACT FROM AUTHOR]

Exploring drug susceptibility is a critical endeavor in the scientific community, setting the stage for advancements in understanding and combating various pathogens. Candida kefyr has emerged as a significant pathogen, particularly affecting immunocompromised individuals with hematologic malignancies and HIV/AIDS conditions. This study aimed to assess the antifungal susceptibility profile of Candida kefyr isolates obtained from clinical samples and dairy products. A total of 134 Candida kefyr yeast isolates were retrieved from three distinct groups: (1) healthy individuals (n = 41), (2) patients (n = 24) including hematologic malignancy (n = 9), HIV/AIDS (n = 7), and diabetes (n = 8), (3) dairy products (milk, yogurt, and cheese, n = 69) stored at −70°C in the Shiraz University of Medical Science. All Candida kefyr isolates were previously identified using conventional and molecular methods. Susceptibility to antifungal drugs, including caspofungin, fluconazole, itraconazole, voriconazole, and amphotericin B, was determined using the microdilution method following CLSI‐M27‐A3 protocols, with results interpreted according to CLSI‐M27‐S4 guidelines. The study emphasizes the clear variation in antifungal susceptibility testing of Candida kefyr strains when compared across different groups, including patients, healthy people, and dairy products. According to the results, across all groups, a high minimum inhibitory concentration of fluconazole is evident, and healthy individuals show the highest minimum inhibitory concentration geometric means (4.0681). Also, 79.1% of the isolates were wild type to amphotericin B, with the lowest minimum inhibitory concentration compared to other antifungals tested. This suggests that amphotericin B was more effective against Candida kefyr. These findings showed fewer susceptibilities of Candida kefyr to both triazole and echinocandin classes of antifungal agents. Additionally, it is noteworthy that individuals without medical conditions exhibited higher minimum inhibitory concentration rates to these antifungal agents in comparison to those with underlying health conditions. Consequently, timely diagnosis and appropriate therapeutic interventions emerge as imperative in the effective management of candidiasis cases. [ABSTRACT FROM AUTHOR]

Candidiasis, which presents a substantial risk to human well‐being, is frequently treated with azoles. However, drug‐drug interactions caused by azoles inhibiting the human CYP3A4 enzyme, together with increasing resistance of Candida species to azoles, represent serious issues with this class of drug, making it imperative to develop innovative antifungal drugs to tackle this growing clinical challenge. A drug repurposing approach is used to examine a library of Food and Drug Administration (FDA)‐approved drugs, ultimately identifying otilonium bromide (OTB) as an exceptionally encouraging antifungal agent. Mechanistically, OTB impairs vesicle‐mediated trafficking by targeting Sec31, thereby impeding the plasma membrane (PM) localization of the ergosterol transporters, such as Sip3. Consequently, OTB obstructs the movement of ergosterol across membranes and triggers cytotoxic autophagy. It is noteworthy that C. albicans encounters challenges in developing resistance to OTB because it is not a substrate for drug transporters. This study opens a new door for antifungal therapy, wherein OTB disrupts ergosterol subcellular distribution and induces cytotoxic autophagy. Additionally, it circumvents the hepatotoxicity associated with azole‐mediated liver enzyme inhibition and avoids export‐mediated drug resistance in C. albicans. [ABSTRACT FROM AUTHOR]

Recent studies have reported an increase in pediatric onychomycosis prevalence worldwide, suggesting that this population may be increasingly affected by the infection. A summary of the epidemiological impact, antifungal treatment options, special considerations for at‐risk subpopulations, and methods to prevent infection and recurrence are discussed. A systematic review of available epidemiological studies found the worldwide prevalence of culture‐confirmed pediatric toenail onychomycosis to be 0.33%, with no significant increases in prevalence over time. A systematic review of studies investigating the efficacy of various antifungals in treating pediatric onychomycosis found high cure rates and low frequency of adverse events with systemic itraconazole and terbinafine; however, the studies are few, dated, and lack impact because of small sample sizes. Comparatively, clinical trials implementing FDA‐approved topical antifungal treatments report slightly reduced cure rates with larger sample sizes. Patients with immunity‐altering conditions, such as Down's syndrome, or those immunosuppressed because of chemotherapy or HIV/AIDS are at a greater risk of onychomycosis infection and require special consideration with treatment. Proper sanitization and hygiene practices are necessary to reduce the risk of acquiring infection. Early diagnosis and treatment of onychomycosis in children, as well as any affected close contacts, are crucial in reducing the impact of the disease. [ABSTRACT FROM AUTHOR]

ABSTRACT Hsp70:J‐domain protein (JDP) machineries play pivotal roles in maintaining cellular proteostasis and governing various aspects of fungal physiology. While Hsp70 is known for its involvement in conferring tolerance to diverse antifungal drugs, the specific contribution of JDPs remains unclear. In this study, we examined the sensitivity of cytosolic JDP deletion strains of budding yeast to amphotericin B (AmB), a polyene antifungal agent widely utilized in fungal disease treatment due to its ability to disrupt the fungal plasma membrane (PM). Deleting Caj1, a PM‐associated class II JDP, heightened susceptibility to AmB, and the protection conferred by Caj1 against AmB necessitated both its N‐terminal J‐domain and C‐terminal lipid binding domain. Moreover, Caj1 deficiency compromised PM integrity as evidenced by increased phosphate efflux and exacerbated AmB sensitivity, particularly at elevated temperatures. Notably, phytosphingosine (PHS) addition as well as overexpression of PMP3, a positive PM integrity regulator, significantly rescued AmB sensitivity of caj1Δ cells. Our results align with the notion that Caj1 associates with the PM and cooperates with Hsp70 to regulate PM proteostasis, thereby influencing PM integrity in budding yeast. Loss of Caj1 function at the PM compromises PM protein quality control, thereby rendering yeast cells more susceptible to AmB. [ABSTRACT FROM AUTHOR]

The current work describes the synthesis, characterization and antimicrobial evaluation of a new series of pyrazolo‐triazaphosphorine derivatives. The synthesized compounds were confirmed by NMR (1H,13C,31P), IR spectroscopy, by elemental analysis and LCMS. The series of phosphorus products were screened for their antifungal activities and for their antibacterial activities. Finally, the antioxidant activity was tested for one of them (2a). The results were compared with biological activities of some drugs and demonstrate that the antibacterial and antifungal activities of 2 a–f, are influenced by the variation of the group R, R' and the donor or attractor effects of the group R′. Likewise, the donor effect of the group in compound 2 e has a positive influence on the antifungal activity and 2 e reacts against Alternaria alternata with the lowest IC50=0.795 μg mL−1 than drug. The phosphorus products can be used as some antibacterial and antifungal agents and one of the compounds(2a) have an excellent antioxidant power. [ABSTRACT FROM AUTHOR]

Background: Dermatophytosis, a prevalent fungal infection, often exhibits treatment failure. It poses ongoing public health concerns, urging exploration of alternative treatment strategies. This study examines eucalyptol's in vitro activity and its interaction with antifungal agents against dermatophyte isolates. Methods: Overall, 489 patients clinically suspected of dermatophytosis were investigated, and the causative agents were molecularly identified. The antifungal activity of eucalyptol, itraconazole, terbinafine, and griseofulvin was assessed according to the guideline of the Clinical and Laboratory Standards Institute (CLSI M38 ed3). The interaction between eucalyptol and the aforementioned antifungals was determined using a checkerboard method. Results: Dermatophytosis was confirmed in 30 out of 489 (6.13%) patients, with a female-to-male ratio of 3:2 and an age range of 8–67 years. The most commonly observed clinical manifestation was tinea corporis (34.21%), and Trichophyton indotineae (n = 14, 46%) was the most common causative agent. Antifungal susceptibility testing revealed that eucalyptol exhibited antidermatophyte properties with minimum inhibitory concentrations (MIC) ranging from 0.78 to 25 mg/mL. Itraconazole demonstrated the lowest geometric mean (GM) value (MIC range: 0.0019–0.25 µg/mL, GM: 0.015 µg/mL), while griseofulvin exhibited the highest GM value (MIC range: 0.125–8 µg/mL, GM: 2.37 µg/mL). The in vitro interaction of eucalyptol with antifungal drugs, except for its combination with terbinafine against two Trichophyton tonsurans isolates resulting in synergistic effects, showed indifference (n = 70, 77.77%) and antagonistic types (n = 18, 20%). Conclusion: Among the evaluated antifungals, itraconazole demonstrated the highest effectiveness against clinical isolates, while eucalyptol alone exhibited a more pronounced effect than when combined with antifungal agents. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cyclosporine A (CSA) dosing has been complicated by considerable intra-patient and inter-patient variability in pharmacokinetics, which is affected by different factors. We aimed to assess the various factors that might affect the CSA dose and its plasma level. Patients and methods: This retrospective study included paediatric cancer patients who underwent allogeneic hematopoietic stem cell transplant at the Children's Cancer Hospital Egypt 57357 from matched related donors with CSA as graft versus host disease prophylaxis. The CSA initial dose was 1.5 mg/kg IV Q12H. Then, it was titrated according to the level and drug toxicity. Cyclosporine A trough levels were assessed two to three times per week using the Emit 2000 cyclosporine-specific assay. Moreover, factors that may affect cyclosporine levels, such as age, sex, weight and the antifungal used, were analyzed to determine their effect on CSA plasma levels. Results: There were 119 patients included in the study. The median age was 10 years; and 43% of them used voriconazole as a prophylactic antifungal. The multivariate analysis revealed that female patients, those >9 years or on voriconazole reached the target level at low initial CSA doses. A higher probability (93%) of reaching the desired plasma level with doses 1.5 mg/kg IV Q12H was observed among patients >9 years, and on voriconazole. While those who were ≤9 years and not on voriconazole required doses >1.5 mg/kg IV Q12H, with an 89% probability of reaching the desired level. Conclusion: This study suggests that the initial CSA dose should consider the patient's age and the antifungal used. Patients >9 years and/or on voriconazole may require lower initial CSA doses and could start with 1.5 mg/kg IV Q12H. [ABSTRACT FROM AUTHOR]

Clotrimazole (CLZ), traditionally an antifungal agent, unveils promising avenues in cancer therapy, particularly in addressing bladder and prostate cancers. In vitro assessments underscore its remarkable efficacy as a standalone treatment, significantly diminishing cancer cell viability. Mechanistically, CLZ operates through multifaceted pathways, including the inhibition of Ca2+-dependent K+ channels, suppression of glycolysis-related enzymes, and modulation of the ERK-p65 signaling cascade, thus underscoring its potential as a versatile therapeutic agent. Our investigation sheds light on intriguing observations regarding the resilience of UM-UC-5 bladder cancer cells against high doses of paclitaxel (PTX), potentially attributed to heightened levels of the apoptosis-regulating protein Mcl-1. However, synergistic studies demonstrate that the combination of Doxorubicin (DOXO) and CLZ emerges as particularly potent, especially in prostate cancer contexts. This effectiveness could be associated with the inhibition of drug efflux mediated by multidrug resistance-associated protein 1 (MRP1), underscoring the importance of exploring combination therapies in cancer treatment paradigms. In essence, our findings shed light on the anticancer potential of CLZ, emphasizing the significance of tailored approaches considering specific cancer types and molecular pathways in drug repurposing endeavors. While further validation and clinical exploration are warranted, the insights gleaned from this study offer promising prospects for enhancing cancer therapy efficacy. [ABSTRACT FROM AUTHOR]

The elaboration of a new family of tetrapodal molecules L1–L3 bearing two pyrazole–tetrazole units is presented. The structure assigned to such molecules was verified by various techniques, including FTIR, NMR, HRMS and elemental analysis. The ability of these tetrapods to inhibit the growth of four fungal strains was examined, and the obtained results showed that they have some antifungal potency in the range of 12–16 mm. The alpha-amylase inhibition activity of these molecules was also evaluated. The obtained IC50 values (1.34 × 10−1–1.2 × 10−2 mg/mL) demonstrated that all compounds are potent enough to inhibit this enzyme much better than the positive control acarbose (2.6 × 10−1 mg/mL). A docking study on the porcine alpha-amylase was performed, and the results were in good correlation with the experimental results. [ABSTRACT FROM AUTHOR]

In 2012, the US Centers for Disease Control and Prevention reported a fungal meningitis outbreak due to Exserohilum rostratum , caused by methylprednisolone administration. Twelve years later, an iatrogenic outbreak of Fusarium meningitis was documented in Mexico after epidural anesthesia. [ABSTRACT FROM AUTHOR]

Varronia curassavica Jacq. is an aromatic species appertaining to the Boraginaceae family and has been mentioned for its numerous traditional uses and pharmacological properties, especially its antimicrobial and anti-inflammatory effects. The aim of the present study was to investigate the phytochemical profile and antifungal activities of the essential oils of V. curassavica, in addition to analyzing the ADMET properties of the majority components. The GC-MS analysis of V. curassavica essential oil (EOVC) comprised 97.36% of total composition, with α-pinene, β-caryophyllene, and bicyclogermacrene (44.46%, 22.87%, and 13.05%, respectively) as the main constituents among other minor/trace constituents. The antifungal activity of EOVC was evaluated against three Candida species and was observed with IC50 > 200 μg/mL. Remarkably, the combination of EOVC with fluconazole significantly reduced the IC50 required for the drug to inhibit C. tropicalis (0.003 μg/mL), C. albicans (0.7996 μg/mL), and C. krusei (17.73 μg/mL). In addition, ADME/Tox studies using α-pinene revealed that the compound poses no toxicity threats but requires caution due to its high permeability to the blood–brain barrier (BBB). Overall, the obtained results suggest that Varronia curassavica essential oil is a potentially good antifungal agent for combating fungal resistance. [ABSTRACT FROM AUTHOR]

Simple Summary: The study focused on the comparison of culturable yeast communities in the feces of two populations of Mew Gulls depending on the breeding site: natural and urban. It was found that the species diversity of yeasts in the feces of gulls from the natural population was significantly higher, while the diversity of pathogenic species in the feces of birds from the anthropogenic population increased. The proportion of strains of pathogens (Candida, Rhodotorula) isolated from the feces of the anthropogenic colony that were resistant to conventional antibiotics was high. Indeed, populations of migratory birds breeding in an anthropogenic area could be involved in the global spread of the "alarming" geography of antifungal resistance, which is an urgent public health problem. Migratory birds play an important role in the spread of yeasts in the environment over long distances and in different geographical regions. Human activities, in turn, have a major impact on the biology of wild birds and, consequently, on the microbial communities for which birds act as carriers and disseminators. We sought to assess the "response" of the diversity of culturable yeasts in the feces of Mew Gulls to the type of nesting site (natural/anthropogenic) during the breeding season from April to October 2023. We isolated and molecularly identified 26 yeast species. The species composition in the feces of birds from the natural habitat was more diverse, and the diversity increased from April to October. In contrast, the diversity in the feces of birds from the urban habitat decreased from April to October. Analysis of susceptibility to conventional antibiotics (fluconazole, voriconazole, and amphotericin B) using the CLSI BMD (Clinical and Laboratory Standards Institute broth microdilution) method in isolated strains of opportunistic Candida (C. parapsilosis and C. tropicalis) and strains of the emerging pathogen Rhodotorula mucilaginosa showed that the proportion of resistant strains was higher in strains isolated from the feces of birds from the anthropogenic population. Mew Gulls that spent their breeding season near a landfill and flew away for wintering appear to be a source for the spread of pathogenic yeasts with resistance against antifungal agents. [ABSTRACT FROM AUTHOR]

Fusarium pseudograminearum (Fpg) is a significant pathogen responsible for fusarium crown rot (FCR) in wheat (Triticum aestivum L.), a disease with devastating impacts on crop yield. The utilization of biocontrol bacteria to combat fungal diseases in plants is a cost-effective, eco-friendly, and sustainable strategy. In this trial, an endophytic bacterial species, designated as SW, was isolated from the roots of wheat. The strain exhibited potent antagonistic effects against Fpg and reduced the FCR disease severity index by 76.07 ± 0.33% in a greenhouse pot trial. Here, 106 colony-forming units (CFUs)/mL of the SW strain was determined to be the minimum dose required to exhibit the antagonism against Fpg. The strain was identified as Bacillus atrophaeus using genome sequencing and comparison with type strains in the NCBI database. Whole-genome sequencing analysis revealed that SW harbors genes for siderophores, antifungal metabolites, and antibiotics, which are key contributors to its antagonistic activity. Additionally, the strain's ability to utilize various carbon and nitrogen sources, successfully colonize wheat root tissues as an endophyte, and form biofilms are critical attributes for promoting plant growth. In summary, these findings demonstrate the ability of Bacillus atrophaeus to control FCR disease in wheat in a sustainable agricultural setting. [ABSTRACT FROM AUTHOR]

The rise in antifungal resistance among medically important fungi causing severe infectious diseases has underscored the urgent need for developing more effective antifungal agents. Growing evidence suggests that compounds combining functional antifungal groups with metals are promising candidates and may well be the key to addressing this global challenge. In this work, a range of new azole-containing tertiary amine compounds were prepared from three N-alkylamine azole skeletons appended with a 2,4-dihalogenobenzene function and one of the five different metal-binding motifs pyridine, quinoline, 8-hydroxyquinoline, 2-methoxyphenol, and 4-bromophenol. The copper(II) binding of these azole compounds was studied by spectrophotometric titrations in buffered aqueous medium to determine the metal binding equilibria and to comparatively characterize the copper(II)-binding ability of the compounds. The activity of all compounds against the opportunistic fungal pathogen Candida glabrata was also evaluated, allowing us to draw important conclusions about structure–activity relationships that will guide the future design of more effective metal-binding antifungal compounds. [ABSTRACT FROM AUTHOR]

Introduction: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% topical solution for up to 24 months. Materials and Methods: Enrolled patients (n = 101) had one target great toenail with mild to moderate distal lateral subungual onychomycosis and applied efinaconazole 10% topical solution to all affected toenails once daily for 18 months (EFN18) or 24 months (EFN24). Efficacy and safety were evaluated at each visit by visual review and mycology sampling. Results: Regarding the target toenail for patients treated for 24 months (EFN24), mycological cure (negative microscopy and culture) was 66.0% at Month 12, increasing to 71.7% at Month 24; effective cure (mycological cure and ≤10% affected nail) was 13.2% at Month 12, rising to 22.6% at Month 24. Mild to moderate application site reactions (symptoms of erythema/scaling) were the only efinaconazole-related reactions, in eight patients (7.9%). No systemic efinaconazole events or drug interactions were found. Patients aged 70 years or more had similar efficacy to younger patients at all time periods and did not show any increased treatment risks. Thinner nails exhibited better clearance versus thicker nails. A higher proportion of patients with Trichophyton mentagrophytes complex infection experienced application site reactions (35.7%), and a higher effective cure was found at Month 24 versus T. rubrum patients. Conclusion: There is a trend of increasing mycological cure and effective cure beyond Month 12 to Month 24, without an increased safety risk. The enrolled population in this trial was significantly older than in the phase III trials, with a greater degree of onychomycosis severity; however, increased age did not appear to reduce the chance of efficacy to Month 24 in this study. Our data suggest that lack of ability to clear nail dystrophy remains a significant problem for patients, rather than any lack of efinaconazole action over long-term treatment periods. [ABSTRACT FROM AUTHOR]

All-trans retinoic acid (ATRA), a derivative of vitamin A, has dramatically altered the treatment landscape for acute promyelocytic leukemia (APL). APL is characterized by the abnormal maturation of myeloid cells, which become arrested at the promyelocyte stage. ATRA effectively induces these cells to differentiate and undergo apoptosis. While generally well-tolerated, ATRA has been associated with rare adverse effects, including hypercalcemia. This case report underscores the importance of vigilant monitoring for ATRA-related side effects, especially when combined with medications which inhibit cytochrome P450 enzymes. Antifungal prophylaxis is common during leukemia treatment. Here, we present a rare instance of hypercalcemia in a pediatric patient attributed to the concurrent use of posaconazole and ATRA. A 15-year-old girl presented with widespread bruising, abnormal uterine bleeding, and pancytopenia. Subsequent investigations led to an APL diagnosis. Classified as standard-risk APL, she received chemotherapy according to the acute myelogenous leukemia-Berlin-Frankfurt-Münster 2004 protocol. After an ATRA course was started in the third month of maintenance treatment, she applied to the hospital with constitutional symptoms of weakness and fatigue on the third day of treatment. In the biochemical tests of the patient, serum Ca concentration was determined to be 16.5 mg/dL. Parathormone was 64.3 pg/mL and the 25-OH D vitamin level was 22 ng/mL and so were within the normal limits. Complete blood count was within the normal range. Although hypercalcemia is a side effect seen in the combined use of ATRA and azole antifungals, to the best of our knowledge, this is the first report in the literature that it was observed in the pediatric age group due to the simultaneous use of posaconazole and ATRA. [ABSTRACT FROM AUTHOR]

This document explores the use of UVF-dermoscopy, a new imaging technique, in diagnosing and distinguishing between Microsporum and Trichophyton infections of the skin. The study found that polarized dermoscopy alone may not be enough to accurately differentiate between these two types of infections, particularly in cases involving glabrous skin. However, UVF-dermoscopy, which reveals green fluorescence, showed potential in distinguishing between the two types of infections. The study acknowledges its limitations and suggests that more research is necessary to validate these findings. [Extracted from the article]

Cryptococcal meningoencephalitis (CM) is an opportunistic fungal infection and a major cause of death among people living with human immunodeficiency virus in sub‐Saharan Africa. 5‐flucytosine (5‐FC) is a unique, brain‐permeable antifungal agent used to reduce mortality from CM and to prevent disease in individuals carrying cryptococcal antigen. 5‐FC has a short plasma half‐life, requiring 6‐hourly oral dosing with an immediate‐release (IR) formulation, a significant challenge in hospital and outpatient settings, risking a lack of compliance. We recently reported the relative bioavailability in fasting conditions of a sustained release (SR) oral pellet formulation of 5‐FC. In this phase I study, we assessed the safety and pharmacokinetic profiles of the new 5‐FC SR formulation in a single dose (2 × 3000 mg), relative to 5‐FC IR tablets (Ancotil®; 1500 mg b.i.d.) in healthy participants in fed conditions. This randomized, two‐period crossover study was conducted in South Africa to confirm the dose of the identified 5‐FC SR formulation for a twice‐daily 5‐FC regimen in patients. Thirty‐six healthy participants were included. All treatments were well tolerated and no serious adverse event was reported. Cmax and AUC(0–t) for the SR formulation (49.2 ± 10.49 μg/mL and 640.4 ± 126.4 h.μg/mL, respectively) were significantly higher than for the IR formulation (36.8 ± 7.61 μg/mL and 456.6 ± 72.8 h.μg/mL, respectively). A physiological based pharmacokinetic model (PBPK) predicted that under fasting conditions, 6000 mg SR pellets would show a good overlap with the IR product (3000 mg b.i.d), thus 6000 mg SR 5‐FC b.i.d. in fasting conditions is recommended. [ABSTRACT FROM AUTHOR]

Polygalacturonase inhibiting proteins (PGIPs) are plant proteins involved in the inhibition of polygalacturonases (PGs), cell-wall degrading enzymes often secreted by phytopathogenic fungi. Previously, we confirmed that PGIP2 from Phaseolus vulgaris (PvPGIP2) can inhibit the growth of Aspergillus niger and Botrytis cinerea on agar plate. In this study, we further validated the feasibility of using PGIP as an environmental and ecological friendly agent to prevent fungal infection post-harvest. We found that application of either purified PGIP (full length PvPGIP2 or truncated tPvPGIP2_5–8), or PGIP-secreting Saccharomyces cerevisiae strains can effectively inhibit fungal growth and necrotic lesions on tobacco leaf. We also examined the effective amount and thermo stability of PGIP when applied on plants. A concentration of 0.75 mg/mL or higher can significantly reduce the area of B. cinerea lesions. The activity of full-length PvPGIPs is not affected after incubation at various temperatures ranging from − 20 to 42 ◦C for 24 h, while truncated tPvPGIP2_5–8 lost some efficacy after incubation at 42 ◦C. Furthermore, we have also examined the efficacy of PGIP on tomato fruit. When the purified PvPGIP2 proteins were applied to tomato fruit inoculated with B. cinerea at a concentration of roughly 1.0 mg/mL, disease incidence and area of disease had reduced by more than half compared to the controls without PGIP treatment. This study explores the potential of PGIPs as exogenously applied, eco-friendly fungal control agents on fruit and vegetables post-harvest. [ABSTRACT FROM AUTHOR]

Background: Many clinicians prescribe antifungal agents to treat canine otitis externa (OE). However, studies evaluating the antifungal effects of N‐acetylcysteine (NAC) and its combinations are limited. Hypothesis/objectives: The aim of this study was to evaluate the antifungal effects of NAC alone and in combination with other antifungal agents against Malassezia pachydermatis isolated from canine OE. Materials and methods: M. pachydermatis samples were collected from 13 dogs with OE. The final concentration of the inoculum suspensions of M. pachydermatis was 1–5 × 106 colony forming units/mL. The concentrations of the test compounds ketoconazole (KTZ), terbinafine (TER), nystatin (NYS) and NAC were 0.02–300 µg/mL, 0.04–80 µg/mL, 0.16–40 µg/mL and 1.25–20 mg/mL, respectively. The minimum inhibitory concentration (MIC) was measured to evaluate the susceptibility of the M. pachydermatis to KTZ, TER, NYS and NAC. The checkerboard testing method and fractional inhibitory concentration index were used to evaluate the effect of NAC in combination with KTZ, TER and NYS against M. pachydermatis. Results: The MIC90 values of M. pachydermatis were 4.6875–9.375 µg/mL, 1.25 µg/mL, 5–10 µg/mL and 10 mg/mL for KTZ, TER, NYS and NAC, respectively. The synergistic effects of KTZ, TER and NYS with NAC were identified in 0/13, 2/13 and 0/13 isolates, respectively. Conclusions and clinical relevance: NAC had an antifungal effect against M. pachydermatis but did not exert synergistic effects when used with KTZ, TER and NYS. Thus, the use of NAC alone as a topical solution could be considered an effective treatment option for canine OE involving M. pachydermatis. [ABSTRACT FROM AUTHOR]

As an important small organic molecule, cyclopropane is widely used in drug design. In this paper, fifty-three amide derivatives containing cyclopropane were designed and synthesized by introducing amide groups and aryl groups into cyclopropane through the active splicing method, and their antibacterial and antifungal activities were evaluated in vitro. Among them, thirty-five compounds were new compounds, and eighteen compounds were known compounds (F14, F15, F18, F20–F26, F36, and F38–F44). Bioassay results disclosed that four, three, and nine of the compounds showed moderate activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively. Three compounds were sensitive to Candida albicans, with excellent antifungal activity (MIC80 = 16 μg/mL). The molecular docking results show that compounds F8, F24, and F42 have good affinity with the potential antifungal drug target CYP51 protein. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidosis (VVC) represents a frequent and cumbersome vaginal infection. Recurrent and/or persistent infections remain common among a significant number of patients despite the use of antifungals. Probiotics offer a promising adjunctive or alternative therapeutic strategy to antifungals in the management of VVC. We aimed to explore and thoroughly examine the various roles and potential applications of probiotics in VVC. A comprehensive literature search was conducted to identify relevant clinical trials and systematic reviews that examine the effectiveness of probiotics in the treatment and prevention of VVC and recurrent VVC (rVVC). Following the initial screening of 4563 articles, a total of 25 clinical studies and seven systematic reviews were finally included in this analysis. The studies reviewed provide a generally positive yet inconsistent view of the efficacy of probiotics in managing VVC, including clinical, mycological response, and prevention perspectives. Nonetheless, fluconazole remains more effective than probiotics in treating VVC, while the combination of the two seems to reduce recurrence and improve symptoms significantly. For prevention, probiotics seem to improve vaginal health and reduce symptoms, while safety and tolerability are consistently reported across the studies, affirming that probiotics represent a low-risk intervention. However, clear conclusions are difficult to establish since relative studies explore different clinical endpoints and follow-up times, variable populations are included, different probiotics are used, and diverse schedules and regimens are administered. We propose that future studies should study the benefit of probiotics in well-defined categories such as (1) treatment with acute probiotics instead of antifungals, (2) adjuvant probiotic therapy together or after antifungals, and (3) VVC recurrence prevention using probiotics. [ABSTRACT FROM AUTHOR]

Introduction: Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis. Methods: Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85 mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded. Results: In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than those for tavaborole (63.5 mm; 39.1 mm), ciclopirox (7.4 mm; 3.6 mm) and all OTC products (range: 10.5–34.2 mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85 mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7 mm, respectively) and OTC products (range: 31.2–57.8 mm and 25.7–47.7 mm, respectively). Conclusions: Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail. [ABSTRACT FROM AUTHOR]

Miconazole nitrate (MNN) is an efficient local antifungal agent with fungistatic and fungicidal activity used for vaginal candidiasis treatment. This study was aimed to formulate and evaluate MNN vaginal in situ thermosensitive mucoadhesive gel to enhance the residence time and potentiate its activity at the infection site. In situ gel formulas of MNN were formulated by employing the cold method using different concentrations of poloxamer P 407 and P188 alone or in combination as thermosensitive polymers and hydroxypropyl methylcellulose K4M (HPMCK4M), HPMCK15M and gellan gum (GG) as mucoadhesive polymers. The developed formulas were evaluated for different in vitro parameters such as gelation time and temperature, clarity, syrangability, pH, content uniformity, viscosity, bioadhesive force, and drug release profile. The results indicated that there is a direct association between the concentrations of poloxamer 188 with gelation temperature while further incorporation of mucoadhesive polymers caused a reduction in gelation temperature. An inverse relationship was observed between polymer molecular weight and concentration with the drug released and a direct relationship with viscosity and mucoadhesive strength. Formula 2 with 18 % P407, 2 % P188 and 0.6% HPMC K4M was selected as the optimal formula with gelation temperature of (34 ±0.033°C), gelation time (4.90 ± 0.012 min), pH value (6.13±0.05), gel spreadability (4.55± 0.02 cm), drug content (99.1 ±0.13 w/v%), mucoadhesion force (0.3136 N) and drug release of (79.5%) over 12 hours. In conclusions and according to obtained results formula 2 could be considered as a doable substitute to ordinary vaginally administered drug delivery systems. [ABSTRACT FROM AUTHOR]

Azole resistance in the pathogenic yeast Candida glabrata is a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding gene CDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactive PDR1 alleles. While the identity of hyperactive PDR1 alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and 2 different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and 2 different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking either SNF2 or SPT7 exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect in PDR1 autoregulation, revealing that these complexes work together to ensure high-level Pdr1-dependent gene transcription. [ABSTRACT FROM AUTHOR]

Candidemia ranks the 4th most prevalence cause of bloodstream infections and stands out as the primary cause of invasive fungal infections among hospitalized patients. Its incidence varies globally from 0.33 to 6.51 episodes per 1000 admissions, representing a major public health burden due to its increasing incidence and high mortality rates. The present research work has been conducted to identify the distribution of Candida species among septicemic patients and to determine the patterns of antifungal susceptibility of Candida species isolates from them in a tertiary care center in South India. Among the 88 Candida isolates, 13 (14.8%) were speciated and identified as C. albicans and 75 (85.2%) were Candida non-albicans. Of them, C. tropicalis (42%) ranks more prevalent. The distribution of virulence factors among 88 Candida isolates revealed that 49 isolates (55.7%) exhibited phospholipase activity, hemolysin production was detected in 68.2% of isolates, biofilm production was demonstrated in 73.9% isolates and coagulase activity was observed in 46.7% isolates. In the present study, Candida species were most sensitive to Amphotericin B (94.3%), which is followed by Caspofungin (93.2%), Voriconazole (92%), Micafungin (90.9%), and the least was observed with Flucytosine (78.4%) and Fluconazole (71.5%). Thus, in order to improve treatment responses, the insights acquired from this research will aid in clinical management and the development of antifungal stewardship recommendations. [ABSTRACT FROM AUTHOR]

Objective In severely burned patients, fungal infections are among the most devastating complications. Candidemia is an important cause of mortality with an increasing incidence despite advances in burn care management. Higher affected body surface area, long intensive care unit (ICU) stay, flame burn, third-degree burn, and previous bacterial infections were associated with the development of candidemia. Candidemia in patients with major burns admitted to an ICU of a tertiary burns center is investigated. Methods Patients hospitalized in the ICU of Adana City Training and Research Hospital from July 1, 2017, to November 10, 2020, were included. The demographic and clinical variables, the Candida species isolated from blood cultures and their antifungal susceptibilities, need for grafting, complications, and rate of mortality are evaluated retrospectively. Patients were grouped as "candidemia" or "noncandidemia" according to whether or not they experienced Candida bloodstream infection. Results A total of 371 patients were included; the mean age was 22.02 ± 20.9 years. Most patients were male (69.5%). The percentage of burned surface area was 25.93 ± 17.6. The mean ICU stay was 16.95 ± 16.3 days. There were 90 candidemia episodes in 69 patients. The most commonly isolated Candida species were C. parapsilosis , C. tropicalis , and C. albicans. The mortality rates in the candidemia and noncandidemia groups were 24.6 and 5.6%, respectively (p < 0.001). Conclusion Adhering to isolation rules, early wound debridement and closure, avoidance of catheters where possible, and avoidance of the early use of broad-spectrum antibiotics are important measures in reducing candidemia in patients with major burns. Candidemia was associated with greater burn surface areas, duration of hospital stay, and larger numbers of interventional procedures. However, previous bacterial infection receiving prolonged antibiotic therapy was the greatest risk factor of candidemia. Culture results are important to select the antifungal agent with high susceptibility, but results are not rapidly available. There is need for early clinical prediction measures to inform early and effective antifungal treatment. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review and meta‐analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. Materials and methods: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta‐analysis. Results: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3–1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667–1.360; p = 0.789; I2 = 73.271) efficacy. Conclusions: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times. [ABSTRACT FROM AUTHOR]

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM. [ABSTRACT FROM AUTHOR]

Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM. [ABSTRACT FROM AUTHOR]

Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 μg/ml) and 7a (38.15 μg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 μg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 μg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells. [ABSTRACT FROM AUTHOR]

The limited availability of efficient treatments for Candida infections and the increased emergence of antifungal-resistant strains stimulates the search for new antifungal agents. We have previously isolated a sunflower mannose-binding lectin (Helja) with antifungal activity against Candida albicans , capable of binding mannose-bearing oligosaccharides exposed on the cell surface. This work aimed to investigate the biological and biophysical basis of Helja's binding to C. albicans cell wall mannans and its influence on the fungicidal activity of the lectin. We evaluated the interaction of Helja with the cell wall mannans extracted from the isogenic parental strain (WT) and a glycosylation-defective C. albicans with altered cell wall phosphomannosylation (mnn4 ∆ null mutants) and investigated its antifungal effect. Helja exhibited stronger antifungal activity on the mutant strain, showing greater inhibition of fungal growth, loss of cell viability, morphological alteration, and formation of clusters with agglutinated cells. This differential biological activity of Helja was correlated with the biophysical parameters determined by solid phase assays and isothermal titration calorimetry, which demonstrated that the lectin established stronger interactions with the cell wall mannans of the mnn4 ∆ null mutant than with the WT strain. In conclusion, our results provide new evidence on the nature of the Helja molecular interactions with cell wall components, i.e. phosphomannan, and its impact on the antifungal activity. This study highlights the relevance of plant lectins in the design of effective antifungal therapies. [ABSTRACT FROM AUTHOR]

Postmortem human subject (PMHS) studies are essential to brain injury research in motor vehicle safety. However, postmortem deterioration reduces the similarity between postmortem test results and in vivo response in material testing of brain tissue and in biomechanical testing of the whole head. This pilot study explores the effect of potential preservatives on brain tissue breakdown to identify promising preservatives that warrant further investigation. To identify preservatives with potential to slow postmortem degradation, samples from an initial PMHS were refrigerated at 10°C to qualitatively compare tissue breakdown from 58 to 152 h postmortem after storage in candidate solutions. On brain tissue samples from a second PMHS, compressive stiffness was measured on six samples immediately after harvest for comparison to the stiffness of 23 samples that were stored at 10°C in candidate solutions for 24 h after harvest. The candidate solutions were artificial cerebrospinal fluid (ACSF) without preservatives; ACSF with a combination of antibiotics and antifungal agents; ACSF with added sodium bicarbonate; and ACSF with both the antibiotic/antifungal combination and sodium bicarbonate. Results were analyzed using multiple linear regression of specimen stiffness on harvest lobe and storage solution to investigate potential differences in tissue stiffness. Qualitative evaluation suggested that samples stored in a solution that contained both the antibiotic/antifungal combination and sodium bicarbonate exhibited less evidence of tissue breakdown than the samples stored without preservatives or with only one of those preservatives. In compression testing, samples tested immediately after harvest were significantly stiffer than samples tested after 24 h of storage at 10°C in ACSF (difference: −0.27 N/mm, 95% confidence interval (CI): −0.50, −0.05) or ACSF with antibiotics/antifungal agents (difference: −0.32 N/mm, 95% CI: −0.59, −0.04), controlling for harvest lobe. In contrast, the stiffness of samples tested after storage in either solution containing sodium bicarbonate was not significantly different from the stiffness of samples tested at harvest. There was no significant overall difference in the mean tissue stiffness between samples from the frontal and parietal lobes, controlling for storage solution. Given the importance of PMHS studies to brain injury research, any strategy that shows promise for helping to maintain in vivo brain material properties has the potential to improve understanding of brain injury mechanisms and tolerance to head injury and warrants further investigation. These pilot study results suggest that sodium bicarbonate has the potential to reduce the deterioration of brain tissue in biomechanical testing. The results motivate further evaluation of sodium bicarbonate as a preservative for biomechanical testing using additional test subjects, more comprehensive material testing, and evaluation under a broader set of test conditions including in whole‐head testing. The effect of antibiotics and antifungal agents on brain tissue stiffness was minimal but may have been limited by the cold storage conditions in this study. Further exploration of the potential for microbial agents to preserve tissue postmortem would benefit from evaluation of the effects of storage temperature. [ABSTRACT FROM AUTHOR]

Provide updated data on the antimicrobial activity and chemical composition of original dry extracts from Lavandula angustifolia herb of Ukrainian origin. The aim - provide new data on the antimicrobial activity of original dry extracts of lavender herb of Ukrainian origin and their chemical composition.. Materials and methods. The objects of the study are dry extracts obtained from the lavender herb with purified water and ethanol solutions (40 and 70 %). The main biologically active substances (BAS) of the extracts were determined by the Thin-layer chromatography and Absorption spectrophotometry methods. The microbiological properties of the test samples of the investigated plant extracts were studied in vitro by the two-fold serial dilutions method. The ability of microorganisms to form a biofilm was determined by the method of adhesion to polystyrene in flat-bottomed plastic plates. The optical density of the initial bacterial suspension was measured on the Densi-La-Meter device, and the density of inoculated bacterial cells on the Multiskan EX photometer at a wavelength of 540 nm. The study of the antimicrobial activity of water and ethanol extracts of lavender herb in a wide range of concentrations was carried out by the agar diffusion method in the "wells" modification, which is commonly used in microbiological practice. Results. Water and water-ethanol extracts of lavender of Ukrainian origin were obtained. Terpenoids (linalool, linylyl acetate and traces of 1,8-cineol), flavonoids (hyperoside, isoquercitrin) and hydroxycinnamic acids (rosmarinic, chlo- rogenic acids) were identified in the extracts. The total content of phenolic compounds is 2.02-2.60 mg/g, flavonoids - 1.46-3.17 mg/g. The largest amount of BAS was extracted with 70 % ethanol. According to the results of experimental studies, the extracts of the lavender herb, obtained by extraction with a water-ethanol solution (40 and 70 % ethanol) at a concentration of 1 mg/ml, have antimicrobial properties against a wide range of infectious agents (S. aureus, E. coli, K. pneumoniae, P. aeruginosa, C. albicans). Studies of the influence of test samples of lavender extracts at a concentration of 1 mg/ml on the ability of microorganisms (S. aureus, E. coli, K. pneumoniae, P. aeruginosa) to form biofilms demonstrated that the highest inhibitory activity against biofilm formation was found in the case of the action of test of a sample of phytoextract obtained by extraction with a water-ethanol solution (40 % ethanol), which accounted for S. aureus - 57.8 %, P. aeruginosa - 66.7 %. A wide spectrum of antimicrobial action was established for the tested lavender phytoextracts under the conditions of application of the concentration range of 10-60 fig/ml. The best spectrum of antimicrobial action and the highest activity corresponds to the lavender extract, obtained by extraction with 70 % ethanol, with the effect depending on the concentration. Conclusion. The lavender herb of Ukrainian origin is a promising and affordable source of potential antimicrobial active pharmaceutical ingredients (API). Water-ethanol lavender extract (70 % ethanol), according to research results, has shown high antimicrobial and antifungal potential. According to preliminary data, antimicrobial activity correlates with the content of phenolic compounds. The obtained results may be useful for the search for original substances for the complex correction of symptoms of neurological deficits of infectious etiology [ABSTRACT FROM AUTHOR]

In this study, rosemary essential oil was encapsulated at different concentrations (0, 5, 10, 15 % w/v) by the electrospraying technique in zein microcapsules (ZME) and evaluated for their antifungal properties. The morphology, functional groups, thermal stability, and crystallinity of the ZME were characterized by SEM, FT-IR, TGA, and XRD, respectively. SEM results showed that the ZME diameter increased from 2.6 to 5.2 µm in response to increasing the rosemary essential oil concentration from 0 to 15%. FT-IR revealed hydrogen reactions between the zein and rosemary essential oil. The TGA results indicated that rosemary essential oil decreased the thermal stability of ZME. The XRD patterns indicated that the ZME was in an amorphous state. The agar well diffusion method in studying the antifungal properties of ZME showed that the ZME had significant antifungal activity against Alternaria alternata (P<0.05). According to the results, ZME that carries rosemary essential oil can actively deter Alternaria alternata on tomatoes. [ABSTRACT FROM AUTHOR]

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The olive tree is crucial to the Mediterranean agricultural economy but faces significant threats from climate change and soil-borne pathogens like Verticillium dahliae. This study assesses the dual role of an onion extract formulation, rich in organosulfur compounds, as both biostimulant and antifungal agent. Research was conducted across three settings: a controlled climatic chamber with non-stressed olive trees; an experimental farm with olive trees under abiotic stress; and two commercial olive orchards affected by V. dahliae. Results showed that in the climatic chamber, onion extract significantly reduced MDA levels in olive leaves, with a more pronounced reduction observed when the extract was applied by irrigation compared to foliar spray. The treatment also increased root length by up to 37.1% compared to controls. In field trials, irrigation with onion extract increased the number of new shoots by 148% and the length of shoots by 53.5%. In commercial orchards, treated trees exhibited reduced MDA levels, lower V. dahliae density, and a 26.7% increase in fruit fat content. These findings suggest that the onion extract effectively reduces oxidative stress and pathogen colonization, while enhancing plant development and fruit fat content. This supports the use of the onion extract formulation as a promising, sustainable alternative to chemical treatments for improving olive crop resilience. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the effects of incorporating 1% and 2% cinnamon oil into a soft liner on the growth of Candida albicans colonies and the material's hardness. Methods: Thirty soft liner specimens were prepared for the disk diffusion and thirty for the hardness test. In each test, the specimens were divided into three subgroups based on the concentration of cinnamon oil: A) 0% (control), B) 1%, and C) 2% by weight. Cinnamon oil was added to the monomer of a heat-polymerized soft liner. C. albicans was cultured on Mueller-Hinton agar, and the diameters of the inhibition zones around the specimens were measured. The Shore A hardness test was conducted using the Shore durometer. Statistical analysis was performed by the independent t-test, one-way ANOVA, and Tukey post-hoc test (a=0.05). Results: The control group showed no inhibition zone. The specimens in Group C exhibited a significantly larger inhibition zone (16.72 ± 0.82 mm) than Group B (12.56 ± 0.82 mm; P < 0.001). The hardness values differed significantly among groups (P < 0.001). Group C demonstrated the highest hardness (48.54 ± 0.95), significantly greater than both Groups B (47.13 ± 0.72; P < 0.05) and A (45.23 ± 0.73; P < 0.05). Conclusions: Adding cinnamon oil improved the antifungal activity and hardness of the soft denture liner. Adding 2% cinnamon oil increased the hardness values to the upper limit of clinical acceptability. Therefore, the 1% concentration is recommended to balance antimicrobial efficacy and maintain optimal mechanical properties of the soft liner. [ABSTRACT FROM AUTHOR]

The rising prevalence of fungal infections and challenges such as adverse effects and resistance against existing antifungal agents have driven the exploration of new antifungal substances. We specifically investigated naphthoquinones, known for their broad biological activities and promising antifungal capabilities. It specifically examined the effects of a particular naphthoquinone on the cellular components of Candida albicans ATCC 60193. The study also assessed cytotoxicity in MRC-5 cells, Artemia salina , and the seeds of tomatoes and arugula. Among four tested naphthoquinones, 2,3-DBNQ (2,3-dibromonaphthalene-1,4-dione) was identified as highly effective, showing potent antifungal activity at concentrations between 1.56 and 6.25 μg mL−1. However, its cytotoxicity in MRC-5 cells (IC50 = 15.44 µM), complete mortality in A. salina at 50 μg mL−1, and significant seed germination inhibition suggest limitations for its clinical use. The findings indicate that primary antifungal mechanism of 2,3-DBNQ might involve disrupting fungal membrane permeability, which leads to increased nucleotide leakage. This insight underscores the need for further research to enhance the selectivity and safety of naphthoquinones for potential therapeutic applications. [ABSTRACT FROM AUTHOR]

Microsporum canis is a dermatophyte that mainly affects dogs and cats. However, it can be transmitted to humans by direct contact. This makes it one of the most frequent causative agents of dermatophytosis in humans, reflecting the frequent human close relationships with pets. Conventional treatment relies on antifungal pharmacological agents. However, errors in application have led to the occurrence of fungal resistance and toxic effects. Consequently, new therapeutic alternatives are needed for M. canis infections. Plant extracts have been explored as phytotherapeutics for the treatment of dermatophyte infections, which prompted an attempt to apply extracts of the ethnopharmacologically important plants Artemisia ludoviciana and Cordia boissieri. Methanolic extracts of these two plants were obtained using a Soxhlet method and were characterised by phytochemical screening. Extracts were evaluated against a M. canis commercial strain (ATCC-11621) using the microdilution method described in the Clinical and Laboratory Standards Institute protocol M38-A, determining its minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC). Subsequently, these concentrations were tested in a human keratinocyte human cell line. Artemisia ludoviciana and C. boissieri extracts showed MIC values of 2,500 and 1,250 µg/mL, and MFC values of 5,000 and 2,500 µg/mL against M. canis, respectively. These extracts did not inhibit HaCaT cell proliferation in vitro. The evaluated extracts showed potential for the treatment of M. canis fungal infections. However, further studies on their phytochemical characterisation, purification, clinical safety and formulation are required. [ABSTRACT FROM AUTHOR]

Background: While selective use of antibiotics for infected pancreatic necrosis (IPN) in acute pancreatitis (AP) is recommended, studies indicate a high rate of inadequate treatment. Methods: A search of PubMed, Scopus, and Cochrane databases was conducted, focusing on primary research and meta-analyses. Data were categorized based on core concepts, and a narrative synthesis was performed. Results: The search identified a total of 1016 publications. After evaluating 203 full texts and additional sources from the grey literature, 80 studies were included in the review. The answers obtained were: (1) Preventive treatment does not decrease the incidence of IPN or mortality. Given the risks of bacterial resistance and fungal infections, antibiotics should be reserved for highly suspected or confirmed IPN; (2) The diagnosis of IPN does not always require microbiological samples, as clinical suspicion or computed tomography signs can suffice. Early diagnosis and treatment may be improved by using biomarkers such as procalcitonin and novel microbiological methods; (3) When indicated, early initiation of antibiotics is a key determinant in reducing mortality associated with IPN; (4) Antibiotics with good penetration into pancreatic tissue covering Gram-negative and Gram-positive bacteria should be used. Routine antifungal therapy is not recommended; (5) The step-up approach, including antibiotics, is the standard for IPN management; (6) Antibiotic duration should be kept to a minimum and should be based on the quality of source control and patient condition. Conclusions: Early antibiotic therapy is essential for the treatment of IPN, but prophylactic antibiotics are not recommended in AP. High-quality randomized controlled trials are required to better understand the role of antibiotics and antifungals in AP management. [ABSTRACT FROM AUTHOR]

Background/Objectives: While multiple studies have investigated antibiotic consumption rates, there are few studies on the consumption of systemic antifungals and antiprotozoals. This study aims to fill this gap by providing a comprehensive analysis of nationwide consumption trends in Kazakhstan over a seven-year period (2017–2023). Methods: Defined daily doses per 1000 inhabitants per day were calculated for systemic antifungals (J02 code of the Anatomical Therapeutic Chemical Classification System (ATC)) and antiprotozoals (P01 code of the ATC). Time series analyses were applied to examine historical trends, evaluate the impact of the COVID-19 pandemic, and make future projections until 2030. Results: The total consumption increased over the study period, with an average annual percent change of 1.11% for antifungals and 5.48% for antiprotozoals. Fluconazole was the most consumed antifungal agent, whereas metronidazole was the most consumed antiprotozoal agent. The COVID-19 pandemic had a positive but insignificant effect on the consumption of antifungals and a negative and also insignificant effect on the consumption of antiprotozoals. Forecast modeling indicates that the future trends in antifungal and antiprotozoal consumption until 2030 will largely remain stable, with the exception of antiprotozoal consumption in the hospital sector, which is projected to decline. Conclusions: These findings offer valuable insights into the development and implementation of targeted antimicrobial stewardship programs in Kazakhstan. [ABSTRACT FROM AUTHOR]

The increasing prevalence of antibiotic-resistant pathogens necessitates the development of novel antimicrobial agents. Herein, PEGylated konjac gum-supported rosin pentaerythritol nanocomposites (KG/PEG/RE PNCs) were synthesized using an environmentally friendly sonochemical method, aiming to explore their potential antibacterial and antifungal properties against a range of pathogens, including Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Aspergillus brasiliensis, and Staphylococcus aureus. An elaborate investigation into the rheological properties of these PNCs highlighted the dependence of viscosity on synthesis parameters such as RE concentration, sonication time, and KG/RE blend ratio with the Higiro model validated as a suitable mathematical model for defining the intricate relationship between experimental and resulting viscosity of PNCs. The integration of machine learning (ML), particularly polynomial regression, enabled the modeling of the complex dynamics influencing PNC viscosity, thus advancing comprehension of PNCs behavior in relation to the synthesis parameters. The modeling facilitated precise formulation to predict PNC viscosity with high accuracy, as confirmed by a mean squared error (MSE) of 3.81 and an R2 of 0.993. Moreover, the PNCs demonstrated broad-spectrum antimicrobial activity, reaching an inhibition plateau during the first week, confirming its efficacy as a versatile antibacterial and antifungal agent. Combining advanced data modeling techniques with biological assessments, this integrated approach represents a step forward in understanding and optimizing polymeric nanostructures. [ABSTRACT FROM AUTHOR]

Objective is to provide crucial epidemiological insights that may aid in early clinical intervention and judicious deployment of antifungal therapies. Methods: This retrospective analysis analyses data on 182 different Candida strains with positive clinical blood cultures obtained from the Microbiology Laboratory of Suining Central Hospital over a period of nine consecutive years. The study involved identification of Candida species and assessment of resistance patterns to fungal drugs. Results: Our analysis revealed that the median age of patients diagnosed with Candidaemia from the 182 strains was 62 years, with a distribution of 63.7% females and 36.3% males. Within the cohort of 182 Candida strains, Candida albicans constituted 32.4%, while non-albicans Candida species comprised 67.6% of the cases. Specifically, Candida tropicalis represented 37.4%, Candida glabrata 12.1%, Candida parapsilosis 11.0%,Candida guilliermondii 3.8%, and both Candida krusei and Candida Dublin accounted for 1.6% each. These Candida species were predominantly identified in intensive care units (ICU), hematology, gastroenterology, neurology centers, and endocrine metabolism units. Conclusion: The findings of this investigation suggest a shift in the prevalence of non-Candida albicans species, notably C. tropicalis, as the predominant cause of Candidaemia at Suining Central Hospital, surpassing C. albicans. Although instances of antifungal resistance are infrequent, there has been a notable rise in resistance to azoles. This study provides important insights into the local epidemiology, which will be essential for informing the selection of empirical antifungal therapy and contributing to the global surveillance of antifungal resistance. [ABSTRACT FROM AUTHOR]

Purpose: Sawdust, a by-product of wood workplaces, poses environmental contamination and reduces workspace efficiency. This research aimed at recycling sawdust from rain tree by incorporating its extracts into gelatin films to create active films with antifungal properties against Aspergillus flavus. Research method: Sawdust was extracted by microwave with various solvents and electrical powers. The extract (0, 0.25, 0.5, 1, and 2%) were then tested for A. flavus inhibition. The extract was also incorporated with gelatin for making wrapped films and tested for inhibition potential on garlic inoculated with A. flavus. Findings: The optimal microwave extraction condition utilized a solvent mixture comprising distilled water and 95% ethanol in a 1:1 v/v ratio, applying 100 watts of electrical power for 30 seconds, repeated 5 times. This method yielded 23.26 mg/g of tannin. Furthermore, the 2% concentration of the extract significantly inhibited both mycelium growth and spore germination of A. flavus (P<0.05) when tested on a petri dish. Additionally, incorporating 2% of the crude extract into gelatin film resulted in the most favorable outcome. This treatment demonstrated the capability to prolong the shelf life of wounded-inoculated garlic for more than 12 days. Research limitations: No limitations were found. Originality/Value: Sawdust originating from a rain tree can be recycled biodegrable actine gelatin films against A. flavus, a field-bomepathogen in garlic. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to investigate the antimicrobial effect of the ethanolic extracts of mint and licorice on Candida albicans and Streptococcus mutans. If the antibacterial and antifungal effects of these plants are observed, they can be introduced as effective plants against oral biofilm microorganisms to replace commercial drugs. They can also be considered cost-effective and innovative solutions to deal with caries. Materials & Methods: Two medicinal plants, mint and licorice, were extracted using ethanol as a solvent following their collection and drying. The antibacterial and antifungal properties of these extracts were evaluated using disc diffusion, well diffusion, and biofilm formation measurement methods on a total of 162 samples. In addition, the Kruskal-Wallis test was employed for statistical analysis, with data processed using SPSS (version 22). A significance level of 5% was maintained across all tests. Results: The analysis of the results in the disc and well diffusion indicated that the concentration of 100 mg/ml of licorice showed the strongest antibacterial effect among different concentrations, and Streptococcus mutans was more susceptible than Candida albicans. Moreover, the results of measuring the amount of biofilm formation demonstrated that the concentration of 100 mg/ml of licorice had the most substantial effect in inhibiting the biofilm of Streptococcus mutans and Candida albicans. Conclusion: Among the examined samples, a concentration of 100 mg/ml of licorice exhibited an antibacterial effect comparable to that of commercial chlorhexidine mouthwash. This finding suggests the potential for further research into the development of an herbal mouthwash based on this extract. [ABSTRACT FROM AUTHOR]

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