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Comparative metabolomics may shed light on host immunity and biology in oral candidiasis (oral thrush). Untargeted metabolomic analyses were performed on oral rinses collected from 26 primary oral candidiasis patients (OT), 12 patients after antifungal treatment (AT), and 12 unaffected individuals (C). Host immune modulation metabolites against oral candidiasis , Candida virulence and antifungal properties were identified. The upregulation of C17 sphinganine, L-leucine, monoacylglycerol, phosphatidylethanolamine, and spermine, in OT and AT groups, highlights the role of host immunity in Candida clearance. The altered sphingolipid levels suggest disrupted membrane integrity and immune function, while dysregulated amino acid, purine, and glutathione metabolism reflect oxidative stress and inflammation. Antifungal metabolites, specifically dichloroacetate, 1-monopalmitin, and undecane-2-one, were significantly upregulated in the OT group; conversely, fatty acids (palmitic amide, linoleamide, stearamide, and pentadecanal) were downregulated. Metabolomic similarities between oral candidiasis and xerostomia were evident, with shared markers such as L-valine, L-leucine, D-proline and 4-hydroxyphenylpyruvic acid. Increases in lipid metabolites, carboxylic acids, and amino acids, particularly L-leucine and hypoxanthine in patients upon resolution of oral candidiasis following antifungal treatment suggests fungal clearance, immune activation and recovery from oxidative stress. Some metabolites identified in oral candidiasis patients have reported roles in oral carcinogenesis, however, the findings remain observational and warrant further validation. Our results demonstrate that oral candidiasis is associated with distinct metabolomic alterations compared with healthy controls, and that antifungal therapy reshapes the oral metabolic profiles via complex host–microbiome–fungal metabolic pathways. The identification of oral candidiasis-associated metabolites also highlights their potential as non-invasive biomarkers and therapeutic targets for oral healthcare.

Hyposalivation is an important problem in elders and could interfere with several oral functions and microbial ecology. While the number of independent elders who retain more natural teeth increases worldwide, few studies examined hyposalivation in this population. Thus, this study aims to examine relationships between hyposalivation, oral health conditions and oral Candida colonization in independent dentate elders and evaluate factors associated with salivary flow and Candida carriage. We conducted a cross-sectional study in fifty-three dentate elders (≥65 years old with at least 4 pairs of posterior occlusal contacts) with no, or well-controlled, systemic conditions. Participants were interviewed for medical history, subjective dry mouth symptoms, oral hygiene practices and denture information. Unstimulated and stimulated salivary flow rates, objective dry mouth signs, gingival, tongue-coating, and root-caries indices were recorded. Stimulated saliva was cultured on Sabouraud-dextrose agar for Candida counts. Candida species were identified using chromogenic Candida agar and polymerase chain reaction. Statistical significance level was set at p<0 . 05 . The results showed that hyposalivation was associated with higher gingival and tongue-coating indices ( p = 0 . 003 and 0 . 015 , respectively), but not root-caries index. Hyposalivation was also associated with higher prevalence of oral Candida colonization ( p = 0 . 010; adjusted OR = 4.36, 95% confidence interval = 1.29–14.72). These two indices and Candida load were negatively correlated with unstimulated and stimulated salivary flow rates. Interestingly, non- albicans Candida species were more prevalent in denture wearers ( p = 0 . 017 ). Hence, hyposalivation is a risk factor for poorer oral health and oral Candida colonization in independent dentate elders. Because of its potential adverse effects on oral and systemic health, hyposalivation should be carefully monitored in elders.

Objective: The aim of the study is to assess the effect of probiotic bacteria on oral Candida counts in cancer patients who are undergoing head- and neck-radiotherapy in a tertiary care center. Study Design: The study was a randomized clinical trial including 90 patients who just completed head- and neck-radiotherapy. Materials and Methods: Participants were randomly allocated into three equal sized groups, i.e., probiotics group, candid group, and combination groups. Oral rinse samples of the patients were collected before and after the intervention for the identification of Candida. The samples were incubated on Sabouraud's Dextrose Agar with Chloramphenicol at 37°C for 48 h, to assess the counts of colony-forming units/milliliter (CFU/ml) of Candida in saliva, and further on chrome agar plates to identify the Candida spp. Data were analyzed using mixed ANOVA to compare mean CFU/ml of Candida among three groups before and after the intervention. Results: A total of 86 patients were included in the final analysis and there was a statistically significant reduction in mean Candida spp. Counts (CFU/ml) after intervention in all the three groups (P = 0.000) and significant reductions identified in both probiotic and combination therapy groups. Apart from reduction in Candida albicans, significant decrease in Candida glabrata and Candida tropicalis was observed after probiotics usage compared to other groups. Conclusions: The present study suggests that probiotic bacteria were effective in reducing oral Candida spp which can be recommended alone or in combination with traditional antifungal agents for effective reduction in oral Candida in head- and neck-radiotherapy patients.

During oropharyngeal candidiasis (OPC), Candida albicans invades and damages oral epithelial cells, which respond by producing proinflammatory mediators that recruit phagocytes to foci of infection. The ephrin type-A receptor 2 (EphA2) detects β-glucan and plays a central role in stimulating epithelial cells to release proinflammatory mediators during OPC. The epidermal growth factor receptor (EGFR) also interacts with C . albicans and is known to be activated by the Als3 adhesin/invasin and the candidalysin pore-forming toxin. Here, we investigated the interactions among EphA2, EGFR, Als3 and candidalysin during OPC. We found that EGFR and EphA2 constitutively associate with each other as part of a heteromeric physical complex and are mutually dependent for C . albicans- induced activation. Als3-mediated endocytosis of a C . albicans hypha leads to the formation of an endocytic vacuole where candidalysin accumulates at high concentration. Thus, Als3 potentiates targeting of candidalysin, and both Als3 and candidalysin are required for C . albicans to cause maximal damage to oral epithelial cells, sustain activation of EphA2 and EGFR, and stimulate pro-inflammatory cytokine and chemokine secretion. In the mouse model of OPC, C . albicans- induced production of CXCL1/KC and CCL20 is dependent on the presence of candidalysin and EGFR, but independent of Als3. The production of IL-1α and IL-17A also requires candidalysin but is independent of Als3 and EGFR. The production of TNFα requires Als1, Als3, and candidalysin. Collectively, these results delineate the complex interplay among host cell receptors EphA2 and EGFR and C . albicans virulence factors Als1, Als3 and candidalysin during the induction of OPC and the resulting oral inflammatory response.

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti- C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans . Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4′,6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid–Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.

Bimekizumab, which has activity against interleukin-17A and interleukin-17F, was compared in a randomized trial with secukinumab, which has activity against interleukin-17A only. Over 48 weeks, treatment with bimekizumab resulted in greater clearance of psoriasis but was associated with oral candidiasis.

The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy—nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and symptoms and changes in salivary IL-17A level compared to standard therapy alone. The study included 59 subjects with a positive microbiological Candida colony number greater than 600 CFU/mL and at least one oral sign or symptom present. Subjects were randomly divided into four groups depending on applied therapy: OLE + NYS group (n = 15), OLE + MIC group (n = 15), NYS group (n = 14), MIC group (n = 15). Therapy duration and clinical monitoring were standardized across all groups. There was no significant difference between the tested groups in Candida spp. colony number or salivary IL-17A levels. In the OLE + NYS group, a significant increase in salivation rate was observed, while a significant decrease in tongue burning was reported in the OLE + MIC group. A significant reduction in burning of the oral mucosa and tongue was observed in the MIC group. No significant differences were found in other clinical signs or symptoms among treatment groups. OLE, as an adjunct to standard antifungal therapy, did not significantly reduce Candida spp. colony number or salivary IL-17A levels. However, in combination with NYS it increased salivation rate, while in combination with miconazole, it significantly decreased tongue burning. Both symptoms are common clinical findings in oral Candida-related disease and suggest that OLE may have supportive potential in the clinical management of these conditions. Further research is needed to explore its potential therapeutic benefits on oral health.

The coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China, in late 2109, and has rapidly spread around the world. Until May 25, 2020, there were 133,521 confirmed COVID-19 cases and 7359 deaths in Iran. The role of opportunistic fungal infections in the morbidity and mortality of COVID-19 patients remains less defined. Based on our multicenter experiences, we categorized the risks of opportunistic fungal infections in COVID-19 patients in Iran. The COVID-19 patients at high risk included those with acute respiratory distress syndrome, in intensive care units, receiving broad-spectrum antibiotics, immunosuppressants or corticosteroid, and supported by invasive or noninvasive ventilation. The patients were most likely to develop pulmonary aspergillosis, oral candidiasis, or pneumocystis pneumonia. Most diagnoses were probable as the accurate diagnosis of opportunistic fungal infections remains challenging in resource-poor settings. We summarize the clinical signs and laboratory tests needed to confirm candidiasis, aspergillosis, or pneumocystosis in our COVID-19 patients.

Background Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients. Methods Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model. Results Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1–35.8%), fluconazole (24.8%, 95% CI: 17.4–32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0–26.0%), voriconazole (20.0%, 95% CI: 1.9–38.0%), miconazole (15.0%, 95% CI: 5.1–26.0%), clotrimazole (13.4%, 95% CI: 2.3–24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5–5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I 2  > 50.00%, P  < 0.01), except for caspofungin (I 2  = 0.00%, P  = 0.65). Conclusions Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin. Registration The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).

Background Head and neck cancer patients receiving chemotherapy and radiation therapy may experience a notable and frequently sudden decline in their oral health. These alterations include oral mucositis that develops during and shortly after treatment, candida infections, trouble speaking, difficulty eating, bleeding gums, and tissue fibrosis. Materials and methods This study aimed to determine the effectiveness of oral care intervention protocol (OCIP) on oral health and oral complications. The experimental group received a structured oral care protocol, and the control group received oral care as per the standard of care of the study setting. These patients were observed every week for up to 6 weeks until the completion of radiation therapy/chemoradiation. An experimental design using a randomized controlled trial was adopted for the study. After providing informed consent, the data were collected from 80 head and neck cancer patients. Results The maximum number of patients, i.e., 42.5% in the experimental group and 32.5% in the control group, were diagnosed with tongue cancer. Most of the participants, i.e., 57.5% in the experimental group and 67.5% in the control group, received chemoradiation as the treatment plan. Among all the oral complications, the median days to develop mucositis ( p  =.015), swallowing difficulty ( p  =.009), and chewing difficulty ( p  =.032) were significantly different from those of the control, indicating that the intervention was effective. As treatment progressed over the weeks, the severity of the oral problems increased in both groups ( p  =.001). Compared with routine care, oral care intervention improved oral health scores among cancer patients receiving head and neck radiation therapy/chemoradiation [F (401.982), p  =.001]. Conclusion These data suggest that the OCIP is clinically helpful in maintaining overall oral health among cancer patients receiving head and neck radiation/chemoradiation. The OCIP effectively delays the incidence of oral complications arising from head and neck radiation therapy/chemotherapy but does not prevent them. The findings of this study can also contribute to providing evidence for the use of an oral care kit, including all evidence-based interventions for patients receiving head and neck radiation/chemoradiation.