Search Results (919)

Non-albicans Candida (NAC) species have emerged as significant opportunistic pathogens due to their reduced susceptibility to antifungal agents combined with their strong ability to form biofilms. The severity of systemic candidiasis caused by NAC species highlights the need for novel antifungal strategies. Retinoids, a group of compounds derived from vitamin A, have been demonstrated to possess significant antifungal activity against the reference strain C. albicans ATCC 2091. This study aimed to assess the antifungal potential of three retinoids, all-trans retinoic acid (ATRA), trifarotene, and tazarotene, against NAC clinical isolates. Various concentrations of the retinoids (from 1 mM to 0.06 mM) were tested in vitro against the growth, adhesion, and biofilm development of NAC species, including Candida glabrata, Candida krusei, and Candida tropicalis, as well as a reference strain of C. auris (CDC B11903). At 1 mM, all three compounds maximally inhibited the growth, adhesion, and biofilm formation of all tested NAC species. At lower concentrations (0.5–0.06 mM), C. krusei remained the most susceptible, especially to tazarotene. Tazarotene also showed a strong inhibitory effect on C. auris and C. glabrata at 0.5–0.25 mM; however, this effect was weaker than that observed against C. krusei. At low concentrations (0.12–0.06 mM), only trifarotene induced a mild but statistically significant inhibition of C. tropicalis growth. Trifarotene at 0.5 mM was also the most effective retinoid in inhibiting C. glabrata and C. tropicalis adherence and biofilm formation, with inhibitory activity maintained even at sub-0.5 mM concentrations (0.25–0.12 mM). Overall, the results suggest that all three retinoids exhibited dose-dependent and species-specific antifungal activity against NAC species, supporting their potential as novel, tailored antifungal agents against drug-resistant Candida strains. Full article

Invasive candidiasis (IC) remains a significant cause of morbidity and mortality among critically ill, hematologic, and neonatal patients worldwide. Rapid and accurate diagnosis is essential to guide timely antifungal therapy and improve outcomes. Among available diagnostic tools, 1,3-β-D-glucan (BDG), a polysaccharide component of the fungal cell wall, has emerged as a key biomarker. BDG assays allow for early detection of probable IC, often preceding positive blood cultures, and offer prognostic information based on serial measurements. Species-specific differences in Candida cell wall composition influence BDG release and diagnostic sensitivity. Candida albicans generally correlates with high BDG levels, whereas Nakaseomyces glabrata, Candida parapsilosis, and Candida auris exhibit variable or lower glucan exposure, limiting assay sensitivity. BDG performance is affected by patient-specific factors, such as prior surgery, transfusions, or coexisting bacterial infections, which may lead to false-positive results. Molecular techniques, including PCR-based assays, provide complementary diagnostic accuracy and species identification, and their combination with BDG testing enhances sensitivity up to 90%. Serial BDG monitoring supports risk stratification and treatment response assessment, with persistent elevations predicting worse outcomes. In neonatal and pediatric populations, optimal cut-off values remain under investigation, highlighting the need for integration with clinical and microbiological data. Overall, BDG represents a valuable adjunct in a multimodal diagnostic workflow, providing both diagnostic and prognostic insights in invasive candidiasis management. Full article

Background: Recurrent vulvovaginal candidiasis (RVVC) is a chronic inflammatory disease primarily caused by Candida albicans (C. albicans). Its pathogenesis remains incompletely understood, and clinical management is challenged by recurrence and drug resistance. Ferroptosis, an iron-dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various infectious and inflammatory diseases. However, its role in RVVC remains unclear, with a particular lack of evidence from clinical samples and animal experiments. Objective: This study aimed to investigate the association between RVVC and ferroptosis. First, we analyzed high-throughput sequencing data from human RVVC samples in the Gene Expression Omnibus (GEO) database to identify the expression profile of ferroptosis-related genes. Second, using an established murine model of chronic vulvovaginal candidiasis (CVVC), we validated changes in ferroptosis-related markers in vaginal tissues in vivo. Furthermore, an in vitro model of C. albicans-infected bone marrow-derived macrophages (BMDMs) was employed to explore the underlying mechanisms. This study provides experimental evidence for elucidating the pathogenesis of RVVC and exploring novel therapeutic strategies. Methods: The RVVC-related gene expression dataset GSE278036 was obtained from the GEO database. Differentially expressed genes (DEGs) were screened using the DESeq2 algorithm and intersected with ferroptosis-related genes from the FerrDb database to identify key targets. A protein–protein interaction (PPI) network was constructed using the STRING database and Cytoscape software, and hub genes were identified via the Betweenness centrality algorithm. Functional and pathway analyses, including gene set enrichment analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways, were performed. Immune infiltration analysis characterized the immune microenvironment in RVVC patients. A CVVC mouse model was established in vivo, and a C. albicans-BMDMs infection model was established in vitro. The ferroptosis inhibitor ferrostatin-1 (Fer-1) was administered to investigate the pathological function and regulatory mechanisms of ferroptosis in RVVC at the molecular, cellular, and tissue levels. Results: Differential analysis identified 3132 DEGs in RVVC, which intersected with ferroptosis-related genes to yield 194 key targets. Among them, 20 hub genes were identified, including ferroptosis regulators and inflammatory factors. Functional enrichment analysis confirmed that these shared targets regulate RVVC pathology through a “ferroptosis-inflammation-immunity” multi-pathway network. Immune infiltration analysis revealed a specific immune disorder in RVVC patients characterized by “activation of the pro-inflammatory innate immune axis and suppression of the adaptive immune axis,” which was closely associated with ferroptosis-related genes. In vivo and in vitro experiments confirmed that C. albicans infection induced ferroptosis in vaginal tissues and macrophages, as manifested by lipid ROS accumulation, Fe²⁺ overload, GSH depletion, downregulation of GPX4 and SLC7A11, upregulation of ACSL4, 4-HNE, and MDA, and mitochondrial structural damage. Macrophages were identified as key target cells for ferroptosis, and their ferroptosis led to impaired antifungal function. Fer-1 treatment significantly inhibited ferroptosis, reduced vaginal histopathological damage and inflammatory cell infiltration, decreased fungal burden, downregulated abnormally elevated inflammatory factors, and restored Th1/Th2 immune balance. Furthermore, Fer-1 preserved macrophage viability and enhanced their antifungal killing capacity. Conclusions: This study provides the first evidence linking RVVC to ferroptosis through a combination of clinical data analysis and experiments, suggesting that ferroptosis is involved in its pathological process. These findings offer a new perspective for elucidating RVVC pathogenesis and developing targeted therapeutic strategies. Full article

Recurrent vulvovaginal candidiasis (RVVC) affects 5–8% of women of reproductive age. Host genetic factors, particularly single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs), may influence RVVC susceptibility by impairing vaginal mucosal antifungal immunity. The aim of this study was to assess the effect of SNPs in genes encoding TLRs on RVVC susceptibility. Τhe distribution of TLR2 Arg753Gln and TLR4 Asp299Gly/Thr399Ile polymorphisms in Greek women, including RVVC (n = 63), first-episode VVC (n = 37), Gardnerella vaginalis vaginitis (GV, n = 36) patients, and healthy controls (n = 61), was investigated using TaqMan SNP genotyping. Genotype and allele frequencies were analyzed under allelic and dominant models, with odds ratios (ORs), 95% confidence intervals (CIs), and linkage disequilibrium assessed. TLR4 Asp299Gly and Thr399Ile heterozygotes were significantly more frequent in RVVC patients compared with controls and affected RVVC susceptibility (OR: 5.57, 95% CI: 1.17–26.56, p: 0.0172; OR: 4.92, 95% CI: 1.02–23.78, p: 0.0306, respectively). No associations were observed for TLR2 Arg753Gln or for any SNP with GV or first-episode VVC. TLR4 variants co-segregated, indicating a haplotype effect. TLR4 haplotypes, rather than TLR2 polymorphism, confer increased RVVC susceptibility, supporting a genetically distinct, mucosal immunity-driven pathogenesis. Larger, ethnically diverse studies with functional assays are warranted to validate these findings and guide personalized prevention and treatment strategies. Full article

Candidemia and invasive candidiasis remain significant causes of late-onset sepsis and mortality in very-low-birth-weight infants, especially in low- and middle-income countries. This narrative review synthesizes studies published between 2008 and 2025 in Latin America, addressing epidemiology, species distribution, antifungal susceptibility patterns, risk factors, therapeutic approaches, and clinical outcomes, with international comparisons. Accordingly, we present a qualitative narrative synthesis (see Methods) rather than a formal year-over-year temporal trend quantification. Globally, five species predominate, namely Candida albicans, C. parapsilosis sensu lato (s.I.), Candida tropicalis, Nakaseomyces glabratus, and Pichia kudriavzevii, with a sustained increase in non-albicans species and growing resistance to fluconazole. In Latin America, the burden varies depending on the hospital setting; C. parapsilosis sensu lato (s.I.) predominates in NICUs, and Candidozyma auris has emerged, associated with nosocomial outbreaks and multidrug resistance. Factors such as extreme prematurity, prolonged catheter use, parenteral nutrition, and antibiotics are consistently associated with the risk of infection. Mortality remains high, influenced by diagnostic delays and species characteristics. Standardized microbiological surveillance, accurate identification, and strategies tailored to each clinical setting are required to improve outcomes in this vulnerable population. Full article

TFF1 is a secretory polypeptide that is typical of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. Originally, TFF1 was discovered as an estrogen-responsive gene in breast cancer cell lines. However, its major physiological expression site is the stomach where it exists mainly in a monomeric form, with minor amounts of homodimeric as well as heterodimeric forms, such as a high-molecular-mass complex with IgG Fc binding protein (FCGBP). For the first time, we characterized different low-molecular-mass forms of TFF1 in human post-menopausal vaginal specimens, i.e., monomeric and dimeric forms. Attempts to identify high-molecular-mass forms of TFF1, such as TFF1-FCGBP, failed. Based on its known anti-inflammatory effects, TFF1 could play an important role in the homeostasis of vaginal microbiota, which is normally predominated by Lactobacillus spp. Due to its lectin activity, TFF1 might also be capable of binding to members of the vaginal microbiota or to vaginal fungal pathogens. This points to a potential role for TFF1 in the vagina’s innate immune defence and could be of clinical relevance particularly after menopause, e.g., for the treatment of bacterial vaginosis or vulvovaginal candidiasis, as here vaginal dysbiosis is often observed as a consequence of estrogen deficiency. Full article

Candida fungi are among the most common human fungal pathogens and invasive candidiasis is one of the predominant invasive mycoses that mainly affects hospitalized patients with suppression of the immunological system and breaches in skin or mucosal barriers. Rapid diagnosis and implementation of appropriate antifungal treatment are key to achieving recovery. In recent years, attention has been drawn to the increasing significance of Candida species other than C. albicans, in particular C. auris and fluconazole-resistant C. parapsilosis. The aim of this work was to present the species spectrum and drug susceptibility of 570 Candida strains isolated from candidemia cases diagnosed in patients hospitalized in southern Poland in the period 2017–2022. The results of Candida-positive blood cultures obtained from five hospitals were analyzed. C. albicans was the most common species, accounting for 42.6% of all strains, followed by Nakaseomyces glabratus (formerly C. glabrata) and C. parapsilosis complex—22.1% and 18.8%, respectively. No C. auris was found. Fluconazole resistance was found in 4.9% of C. albicans strains, 34.7% of N. glabratus strains, and 8.7% of C. parapsilosis complex strains. Full article

Candida species are frequently detected in bile cultures during endoscopic retrograde cholangiopancreatography (ERCP), but their clinical significance and the value of antifungal treatment remain unclear. We performed a retrospective single-center cohort study of adults with growth of Candida species from bile cultures collected by ERCP performed between 2010 and 2023. We compared inpatients who received vs. those who did not receive antifungals within one week of ERCP and a subgroup with acute cholangitis. The primary outcome was a composite of death and invasive candidiasis within one year. Secondary outcomes included death, invasive candidiasis, and rehospitalization. Inverse probability of treatment weighting (IPTW) was performed using baseline characteristics. Adjusted hazard ratios and odds ratios were calculated. Among 197 inpatients, 51 (25.9%) received antifungals. At one year, the primary outcome occurred in 23 of 51 patients (45.1%) receiving antifungal therapy and in 67 of 146 patients (45.9%) who did not; the IPTW-adjusted hazard ratio was 0.93 (95% confidence interval 0.69–1.27; p = 0.66). No significant differences were seen in the acute cholangitis subgroup (n = 117). In this study, antifungal therapy was not associated with improved survival, lower rates of invasive candidiasis, or fewer readmissions. Findings support a conservative, stewardship-oriented approach to managing Candida-positive bile cultures in the absence of invasive disease. Full article

Background: Oral complications are common in cancer patients, especially those with head and neck cancers. Patients who have been exposed to radiotherapy for their head and neck cancers endure considerable short- and long-term complications. Methods: A scoping review following the ScR and OSF registries protocol was conducted in MEDLINE/PubMed, Embase, Cochrane, Scopus, LILACS, and Web of Science to identify relevant articles from 1993 to 30 June 2025. Inclusion criteria covered clinical trials, case series, prospective and retrospective studies, and diagnostic investigations. Figures were taken from the treated patients after their consent. Results: Radiotherapy-induced oral complications include, but are not limited to, periodontitis, oral mucositis, xerostomia, fibrosis and trismus, dental caries, oropharyngeal candidiasis, burning mouth syndrome, and osteoradionecrosis. Conclusions: An integrated, collaborative, multidisciplinary approach to managing these patients should be implemented to reduce these toxicities and their impact on patients’ vitality and quality of life. This review discusses the main oral complications of radiotherapy in patients with head and neck cancers and summarizes the updated management approaches for these complications. Full article

Candida albicans is the primary agent of acute vulvovaginal candidiasis (VVC) and its recurrent form (RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins (BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we aimed to evaluate the immune signaling pathways governing the temporal regulation of epithelial BD-1 and BD-3 expression during vaginal infection. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3/IL-1β signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3 and identifying NLRP3/IL-1β and IL-17RA signaling as key pathways shaping mucosal defensin expression. Full article

Endocytic trafficking in Candida albicans is a fundamental cellular process that is crucial for its secretion, filamentation, and virulence-related processes. We have previously demonstrated that loss of the key endocytosis-related C. albicans gene END3 disrupts clathrin-mediated endocytosis, leading to impairments in actin patch formation, filamentation, biofilm formation, cell wall integrity, and extracellular protease secretion. The end3 null mutant also exhibits altered antifungal susceptibility and reduced host-cell damage in an in vitro keratinocyte infection model. To ascertain whether endocytosis is required for virulence in vivo, we assessed virulence of the C. albicans end3 null mutant in a murine model of disseminated candidiasis. After infection via the tail vein, and analysis of host survival over 28 days, the end3 null mutant was markedly hypovirulent compared to corresponding control strains. These results indicate that endocytosis mediated by END3 in C. albicans contributes to pathogenesis in vivo. Full article

Background: Vaginal infections often present with overlapping symptoms and involve single or multiple pathogens. However, the relationship between clinical symptoms and molecularly defined vaginal pathogen profiles, especially in multi-pathogen infections, remains poorly characterized in a routine care setting. This study exams the connection between vaginal symptoms and pathogen profiles among women with vaginitis in Northern Vietnam. Methods: We conducted a multicenter cross-sectional study of women with vaginitis at Bac Ninh CDC and Hanoi Obstetrics and Gynecology Hospital between December 2023 and December 2024. Baseline demographics and clinical symptoms were assessed by physicians. Vaginal swabs were collected for pH measurement and pathogen detection using multiplex real-time PCR. The correlation was analyzed using logistic regression in GraphPad Prism v10.1.1. Results: Among 289 symptomatic women, abnormal vaginal discharge and itching were the most common symptoms. Gardnerella vaginalis was the most commonly detected pathogen, occurring alone or in combination with Candida albicans, Mycoplasma hominis, and other genital pathogens. Multi-pathogen infection was associated with abnormal vaginal discharge (OR = 5.44), itching (OR = 2.13), and elevated vaginal pH (OR = 4.70). Women at the tertiary hospital showed greater symptom burden (OR = 1.75) and higher prevalence of multi-pathogen infections (OR = 9.75) than those attending the provincial CDC. Conclusions: Multiplex real-time PCR combined with simple clinical indicators (symptom clustering and vaginal pH) provides practical diagnostic value for identifying multi-pathogen infections in symptomatic women. This integrated approach may support more accurate etiologic diagnosis and guide rational testing strategies, particularly in resource-limited settings. Full article

This study analyzes the evolution and spatial distribution of cervical cancer mortality. Furthermore, it develops a dynamic simulation model for estimating the evolution of the disease up to 2040. This manuscript details an ecological and retrospective study that analyzed official mortality, morbidity, and population data from the 58 municipalities that constitute the state of San Luis Potosi. We used Moran’s index, linear correlation, structural equation modeling, Excel predictions, and Vensim PLE x64 simulation software to conduct this study. The evolution of deaths from cervical cancer shows a downward trend; mortality follows a clustered distribution pattern, and it is not random. The structural model showed standardized regression coefficients of 0.68 between syphilis cases and cervical cancer cases, with a coefficient of 0.35 for deaths; candidiasis cases with cervical cancer at a coefficient of 0.25 and with deaths from the same disease at a coefficient of 0.46. The coefficients of determination for cervical cancer cases and deaths were 0.74 and 0.91, respectively. This shows that these co-infections—syphilis and candidiasis—are a risk factor for cervical cancer mortality. The estimated mortality rates per 100,000 inhabitants for 2025, 2030, 2035, and 2040 were 5.5, 5.1, 4.8, and 4.4, respectively. The prediction indicates an increase in the number of CC cases and deaths from this cause. Full article

Background: Vulvovaginal candidiasis (VVC) is a significant public health concern characterized by increasing incidence and challenges in treatment. However, most studies investigating Candida spp. virulence factors and antifungal susceptibility predominantly rely on in vitro assays. While these assays are highly reproducible, they do not accurately replicate the complex vaginal microenvironment. To address this limitation, we developed an ex vivo model using porcine vaginal mucosa and a physiologically relevant volume of simulated vaginal fluid (SFV) to better mimic human vaginal conditions. Methods: Biofilm formation and fluconazole activity were assessed using the reference strain Candida albicans ATCC 90028 and two clinical isolates associated with VVC. Results were expressed as colony-forming units (CFU) and directly compared with in vitro assays conducted in Sabouraud dextrose broth (SDB) and SVF. Results: CFU analysis revealed that the ex vivo vaginal mucosa model supported more robust biofilm development, with counts ranging from 6.67 × 10⁷ to 7.20 × 10⁷ CFU/mL, compared to the in vitro SDB assay (3.58 × 10⁷ to 4.5 × 10⁷ CFU/mL). This suggests enhanced fungal growth under tissue-based conditions. Moreover, fluconazole achieved greater biofilm eradication in the ex vivo model (>70%) compared to the in vitro SDB assay (≤34.50%), which may indicate increased antifungal activity within a physiologically relevant environment. Conclusions: The ex vivo vaginal mucosa model offers a physiologically relevant platform for supporting C. albicans biofilm development and serves as a valuable alternative for preclinical screening of antifungal agents. Full article

Background: Ocular candidiasis is a serious metastatic complication of candidemia that may lead to irreversible visual impairment. Although recent meta-analyses suggest an overall prevalence of approximately 10%, real-world data from Southeast Asia remain limited. Regional differences in Candida species distribution, antifungal resistance patterns, and health-care resources may influence both the incidence of ocular candidiasis and the utilization of ophthalmic evaluation in routine practice. Methods: We conducted a retrospective cohort study of patients aged ≥15 years with candidemia at a 900-bed tertiary-care university hospital in southern Thailand between January 2014 and August 2025. Only the first episode of candidemia per patient was included. Ophthalmic evaluation was defined as a dilated funduscopic examination performed by an ophthalmologist within 4 weeks of candidemia onset. Ocular candidiasis was classified as Candida chorioretinitis or Candida endophthalmitis according to established definitions. Multivariable logistic regression was used to identify factors independently associated with receipt of ophthalmic evaluation. Results: Among 337 patients with candidemia, 67 (19.9%) underwent ophthalmic evaluation. Ocular candidiasis was diagnosed in 9 of 67 evaluated patients (13.4%), corresponding to an overall incidence of 2.7% in the entire cohort. Five patients (7.5%) had Candida chorioretinitis and four (6.0%) had Candida endophthalmitis, including two concordant and two discordant cases. Visual symptoms were assessable in 35 patients, among whom only 4 (11.4%) reported visual complaints; most patients with ocular candidiasis were asymptomatic at diagnosis. Candida albicans and Candida tropicalis accounted for 55.6% and 44.4% of ocular candidiasis cases, respectively, and bilateral ocular involvement was observed in 77.8%. Ophthalmic findings led to modification of antifungal therapy in 7 of 9 patients with ocular candidiasis (77.8%), most commonly through addition or switching to an azole-based regimen and/or prolongation of treatment duration. In multivariable analysis, vasopressor use at candidemia onset was independently associated with a lower likelihood of ophthalmic evaluation, whereas early infectious diseases consultation was independently associated with increased odds of receiving ophthalmic evaluation. Conclusions: In this Southeast Asian cohort, ophthalmic evaluation was infrequently performed but yielded clinically actionable findings and frequently altered antifungal management. The observed incidence of ocular candidiasis among examined patients was higher than that reported in Western countries. Underutilization of an ophthalmic evaluation appears to reflect illness severity and care pathway factors rather than low disease burden, suggesting that the true incidence of ocular candidiasis may be underestimated. Integrating ophthalmic evaluation into standardized candidemia care pathways may improve detection of ocular involvement, particularly in resource-limited settings. Full article