Search Results (77)

Objectives: Stomatitis is a broad term for oral mucosal inflammation, and oral candidiasis represents one of its common subtypes caused by fungal infection. This study aimed to investigate the relationship between oral candidiasis and reduced salivary flow in patients diagnosed with stomatitis and to identify clinical predictors of oral candidiasis. Methods: A total of 259 patients (mean age 59.77 ± 15.93 years; range 10–87 years; 201 females) with stomatitis were evaluated for oral candidiasis through Candida albicans culture testing. Clinical characteristics were compared between Candida-positive and Candida-negative groups. Unstimulated salivary flow rate (UFR) and stimulated salivary flow rate (SFR) were measured to assess xerostomia. Results: Among the 259 patients, 81 (31.3%) were diagnosed with oral candidiasis. Patients with candidiasis were significantly older (64.25 ± 14.66 years) than those without (57.73 ± 16.10 years; p = 0.002). Both UFR (0.36 ± 0.32 vs. 0.47 ± 0.28 mL/min, p = 0.006) and SFR (1.21 ± 0.68 vs. 1.41 ± 0.69 mL/min, p = 0.032) were significantly lower in the candidiasis group. The prevalence of xerostomia was significantly higher among Candida-positive patients, based on UFR ≤ 0.2 mL/min (49.4% vs. 18.5%, p < 0.001) and SFR ≤ 0.7 mL/min (27.2% vs. 10.7%, p < 0.001). The predictive accuracy for oral candidiasis was 62.2% based on age (AUC = 0.622; cutoff 64.50 years), 65.8% for UFR (AUC = 0.658; cutoff 0.335 mL/min), and 58.7% for SFR (AUC = 0.587; cutoff 1.150 mL/min). In the generalized linear model, xerostomia, as defined by UFR, was a significant predictor of oral candidiasis (B = 0.328, 95% CI: 0.177–0.480, p < 0.001). Conclusions: Oral candidiasis in patients with stomatitis was more strongly associated with decreased UFR than with aging alone. Among the factors assessed, reduced unstimulated salivary flow may serve as a useful clinical indicator for predicting oral candidiasis, particularly in elderly individuals. Full article

The global burden of fungal infections is rising at an alarming rate, with superficial, cutaneous, and mucosal mycoses among the most prevalent. Conventional treatments rely on oral and topical antifungal agents; however, these therapies are often limited by adverse effects, toxicity, frequent recurrence, and poor patient adherence due to prolonged treatment regimens. Moreover, the emergence of antifungal resistance and multidrug-resistant species such as Candidozyma auris and Trichophyton indotineae highlights the urgent need for alternative therapeutic strategies, such as antimicrobial photodynamic therapy (aPDT). aPDT is based on photophysical and photochemical processes involving a photosensitizer (PS), a light source, and molecular oxygen. When combined, these elements generate reactive oxygen species that selectively destroy microbial cells. In this review, we explore various PSs and their effectiveness in aPDT against infections caused by dermatophytes, Candida spp., and other pathogenic fungi. Promisingly, aPDT has demonstrated antifungal activity against both susceptible and resistant strains. In addition, aPDT has been successfully used in cases of mycoses unresponsive to conventional therapies, showing favorable clinical outcomes and overall safety. Current evidence supports aPDT as a valuable strategy for the management of cutaneous, mucosal, and superficial fungal infections and as a potential strategy to combat antifungal resistance. Full article

Lactoferrin (LF) is a natural glycoprotein with strong antimicrobial, immunomodulatory, and nutritional potential and is widely present in milk and mucosal secretions. This paper aims to review the current knowledge on the application of lactoferrin and its bioactive peptides in the context of fungal infections caused by Candida spp., focusing on newborns and pregnant women as high-risk groups. The multifaceted mechanisms of LF action are discussed, including iron chelation, destabilization of fungal cell membranes, and modulation of the immune response. Additionally, data demonstrating the effectiveness of LF in the prevention and supportive treatment of Candida spp. infections are presented. Full article

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

Background/Objectives: The interleukin 17 (IL-17) family, known for its proinflammatory properties, is important in immune responses against bacterial and fungal infections. To exert its immune function, the IL-17 family typically binds to IL-17 receptor (IL-17R) to facilitate signal transduction. Methods: This study identified, cloned and analyzed seven IL-17 and nine IL-17R family members in snakeheads. Results: A duplication event occurred in snakehead IL-17s and IL-17Rs, but bioinformatics analyses indicated that these genes were conserved in both protein domains and evolutionary processes. Tissue distribution analysis revealed that IL-17s/IL-17Rs were widely distributed in the detected tissues, with relatively high expression levels in immune tissues. Upon Nocardia seriolae stimulation, most members were expressed, particularly IL-17C2, IL-17D, IL-17N, IL-17RA1, IL-17RA2, IL-17RC1, and IL-17RE1, which were significantly upregulated in gill and intestine. Conclusions: These results suggested that IL-17s and IL-17Rs played a crucial role in mucosal immunity against bacterial infection, providing insights into immunoprophylactic strategies for bacterial diseases in aquaculture. Full article

Background/Objectives: The oral cavity has garnered increasing attention as a site for viral infection and related pathological manifestations in coronavirus disease-19. This article aims to provide a comprehensive overview of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-related oral manifestations, including taste disturbances, oral lesions and osteonecrosis. Methods: A search was conducted up to September 2024 according to PRISMA (Preferred Reporting Items for Systematic Reviews) guidelines using the databases PubMed and Scopus. All the observational, case-series, case-report and cross-sectional studies written in English on oral manifestations related to COVID-19 disease and long-COVID disease were included. All other types of studies and studies based on oral manifestation after COVID-19 vaccination and oral impairment due to lockdown were excluded. The risk of bias of included studies was assessed using the Joanna Briggs Appraisal checklist. Results: A total of 104 articles including 23 case-report, 15 case-series, 8 case-control, 18 cohort and 40 cross-sectional studies were selected. The results showed that patients with COVID-19 were found to have a significantly higher prevalence of xerostomia (45–74%) and dysgeusia (32–59%) compared to non-infected individuals. Regarding oral mucosal lesions, ulcers, candidiasis and herpes simplex infections were frequently observed. As for osteonecrosis, a significant number of patients with COVID-19-associated rhinomaxillary mucormycosis presented with maxillary osteonecrosis due to fungal infection, primarily mucormycosis. The methodological quality of most of the studies was moderate/high. Conclusions: COVID-19 has been associated with a range of oral manifestations. The complex interplay of viral infection, immune response, medication use and stress likely contributes to these oral complications. Early recognition and management of these oral manifestations are crucial for improving patient outcomes and developing targeted preventive and therapeutic strategies for COVID-19-related oral health issues. Full article

Acute invasive fungal rhinosinusitis (AIFR) is a rare, severe, and life-threatening opportunistic infection associated with high mortality and morbidity. Rapid and accurate diagnosis and treatment are crucial for survival and effective disease management. Diagnosing AIFR is challenging because no single pathognomonic feature exists other than surgical biopsy showing fungal angioinvasion and necrosis. This narrative review focuses on the diagnostic challenges and pitfalls, emphasizing the critical clinical value of magnetic resonance imaging (MRI) for early diagnosis of AIFR. It includes selected cases that illustrate the significance of MRI. When AIFR is suspected, clinical symptoms, nasal endoscopy, blood samples, and facial computed tomography all provide non-specific information. In contrast, MRI can identify signs of devitalized sinonasal mucosa consistent with AIFR. The absence of mucosal enhancement on T1-weighted images, combined with restricted diffusivity, are characteristic MRI features of AIFR. The cases presented underscore the usefulness of MRI in supporting clinical suspicion of AIFR and accurately determining its topography, thereby guiding early surgical biopsies and debridement. In suspected cases of AIFR, MRI serves as a valuable supplementary, non-invasive tool to help determine whether prompt surgical biopsy or debridement is necessary, thereby enhancing early diagnosis and improving survival rates. Therefore, the threshold for conducting an MRI in these cases should be low. Full article

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the paranasal sinuses with a yet unknown etiology. As studies continue to elucidate the disease’s heterogeneity inflammatory profile and presentation, there is a growing interest in the influence of the nasal microbiome on disease pathogenesis and chronicity. The sinus microbiota appear dominated by the Staphylococcus and Corynebacterium genera; known upper airway pathogens, such as Haemophilus influenza, are present in the upper airways of healthy individuals, though at relatively lower abundances than in CRS patients. Viral culprits may induce an unhindered local immune response that contributes to the recurrence and chronicity of inverted papillomas—benign mucosal lesions with the propensity for local destruction and malignant transformation that can be found in patients with a history of nasal infection. The persistence of inverted papillomas warrants investigation into their pathogenesis and how they may contribute to a nasal landscape promoting the chronicity of CRS. Further investigation is needed to uncover the interplay between resident microbiota and viral, fungal, and immunological influence. Discerning between ‘healthy’ and ‘diseased’ sinonasal microbiomes and ‘keystone’ species could shed light on CRS etiology and provide the opportunity for CRS treatment tailored to an individual’s microbiome. This review aims to explore the interrelation of microbial residents in the pathogenesis and chronicity of the diseased sinonasal environment. Full article

Microbiological communities have a significant impact on health and disease. Candida are ubiquitous fungal pathogens that colonize the mucosal surfaces of the genital, urinary, respiratory, and gastrointestinal tracts, as well as the oral cavity. If the immune system is inadequate, then Candida infections may pose a significant threat. Due to the limited number of clinically approved drugs for the treatment of Candida albicans-based infections and the rapid emergence of resistance to the existing antifungals, a novel series of isoxazole-based derivatives was synthesized and evaluated in vitro for their anti-Candida potential. Two compounds, PUB14 and PUB17, displayed selective antifungal activity without negatively affecting beneficial microbiota, such as Lactobacillus sp., at the same time. Moreover, these compounds exhibited significantly lower cytotoxicity in comparison to conventionally applied local antimicrobial (octenidine dihydrochloride), indicating their potential for safe and effective clinical application in conditions such as vulvovaginal candidiasis. The selective antifungal activity of PUB14 and PUB17 against C. albicans, coupled with its absence of antibacterial effects and minimal cytotoxicity towards HeLa cells, suggests a targeted mechanism of action that warrants further investigation. Consideration of the need to search for new antifungal agents and the discovery of an antifungal potential drug that does not inhibit lactobacilli growth could be a potential strategy to prevent and combat vulvovaginal candidiasis. This striking capacity to eradicate biofilm formed by Candida reveals a new approach to eradicating biofilms and sheds light on isoxazole-based derivatives as promising anti-biofilm drugs. Full article

Leukemias and lymphomas, encompassing a spectrum of hematologic malignancies, often exhibit manifestations in various tissues and organs, including the ears, nose, and throat (ENT) region, extending beyond the typical sites of bone marrow and lymph nodes. This manuscript explores these interactions, considering disease-related symptoms and treatment effects. ENT symptoms, such as otalgia, hearing loss, and nasal obstruction, may arise from direct infiltration or treatment complications, with chemotherapy-induced ototoxicity being particularly characteristic. Furthermore, immunotherapy complications, including cytokine release syndrome and mucosal irritation, can also contribute to ENT symptoms. Additionally, targeted therapy and radiotherapy can lead to mucosal dryness, dysphonia, and radiation-induced otitis media. Patients with hematologic malignancies are especially vulnerable to various ENT infections, including bacterial, viral, and fungal infections, due to compromised immunity resulting from both the disease and its treatments. Conditions such as rhinosinusitis, otitis media, and pharyngitis pose significant management challenges. Moreover, patients undergoing hematopoietic stem cell transplantation (HSCT) face unique ENT considerations, including mucositis, opportunistic infections, and graft-versus-host disease in cases of allogeneic HSCT. These patients require specialized pre-transplant evaluations, meticulous post-transplant surveillance, and tailored assistance to mitigate complications. This manuscript underscores the importance of a multidisciplinary approach that integrates diagnostics, pharmacological interventions, and supportive care to address both disease-related and treatment-induced ENT manifestations. Further research is needed to refine management strategies and improve outcomes in this complex clinical population. Full article

Psoriasis is a chronic inflammatory skin disease with complex pathogenesis and variable severity. Performed studies have indicated the impact of vitamin D3 deficiency on the pathogenesis of psoriasis and its severity. However, there is no clear evidence of the influence of the mucosal microbiome on the onset and progression of psoriasis. This review aims to present the current evidence on the role of vitamin D3 and colonization of the oral mucosa by Candida yeast-like fungi in the pathogenesis of psoriasis. Candida albicans is a common yeast that can colonize the skin and mucosal surfaces, particularly in individuals with weakened immune systems or compromised skin barriers. In psoriasis, the skin’s barrier function is disrupted, potentially making patients more susceptible to fungal infections such as Candida. Since patients with psoriasis are at increased risk of metabolic syndrome, they may experience the vicious circle effect in which chronic inflammation leads to obesity. Vitamin D3 deficiency is also associated with microbiological imbalance, which may promote excessive growth of Candida fungi. Under normal conditions, the intestinal and oral microflora support the immune system. Vitamin D3 deficiency, however, leads to disruption of this balance, which allows Candida to overgrow and develop infections. Full article

Denture stomatitis (DS) is a very common disease in wearers of removable complete and partial dentures with a worldwide prevalence in the range of 20–67%. Both industrially developed and impoverished nations are affected by the illness. DS is often associated with ill-fitting dentures or a fungal infection with Candida spp. Candida is normally found in the oral cavity microbiota, but it can be harmful to the health of elderly people with underlying diseases. Therefore, the purpose of the present study is to offer the most recent information about the epidemiology, etiology, and global distribution of Candida species associated with DS through a systematic review. Several databases, including Medline, Web of Science, and Scopus, were used to conduct an extensive search of the literature published in the previous 20 years. The selection of studies was performed by two authors. The extracted data were as follows: author, year of publication, country, sample, frequency of DS, method of diagnosing stomatitis, species of Candida, risk factors, and etiology of the disease. The JBI Critical appraisal tools were used to assess the quality of the studies. Eventually, twenty-eight studies were included in the systematic review. Twenty-one studies investigated DS, while seven studies examined Candida colonization in patients using removable dentures. The results show that the main causes of DS include the type of dentures, continuous wearing of dentures, and the formation of a Candida biofilm, which is facilitated by poor dental hygiene. Additionally, previous studies have pinpointed the significance of the salivary flow, saliva composition, and salivary pH. The findings of the current review indicate that it is crucial to monitor denture wearers for the appearance of DS, especially the patients whose immunity has been impaired due to a systemic condition. Finally, frequent follow-ups should include a clinical examination and microbial swabs of the palatal mucosa and the mucosal surface of the denture. Full article

In recent years, the incidence of fungal infections in humans has increased dramatically, accompanied by an expansion in the number of species implicated as etiological agents, especially environmental fungi never involved before in human infection. Among fungal pathogens, Candida species are the most common opportunistic fungi that can cause local and systemic infections, especially in immunocompromised individuals. Candida albicans (C. albicans) is the most common causative agent of mucosal and healthcare-associated systemic infections. However, during recent decades, there has been a worrying increase in the number of emerging multi-drug-resistant non-albicans Candida (NAC) species, i.e., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris, and C. ciferrii. In particular, Candida ciferrii, also known as Stephanoascus ciferrii or Trichomonascus ciferrii, is a heterothallic ascomycete yeast-like fungus that has received attention in recent decades as a cause of local and systemic fungal diseases. Today, the new definition of the S. ciferrii complex, which consists of S. ciferrii, Candida allociferrii, and Candida mucifera, was proposed after sequencing the 18S rRNA gene. Currently, the S. ciferrii complex is mostly associated with non-severe ear and eye infections, although a few cases of severe candidemia have been reported in immunocompromised individuals. Low susceptibility to currently available antifungal drugs is a rising concern, especially in NAC species. In this regard, a high rate of resistance to azoles and more recently also to echinocandins has emerged in the S. ciferrii complex. This review focuses on epidemiological, biological, and clinical aspects of the S. ciferrii complex, including its pathogenicity and drug resistance. Full article

Zoonotic sporotrichosis, a subcutaneous mycosis caused by Sporothrix brasiliensis, has become hyperendemic and a serious public health issue in Brazil and an emerging disease throughout the world. Typical sporotrichosis is defined as fixed or lymphocutaneous lesion development, however, reports of atypical presentations have been described in hyperendemic areas, which may result in a worse prognosis. Thus, considering an increase in atypical cases and in more severe extracutaneous cases and hospitalizations reported in Brazil, we aimed to perform a systematic review to search for hypersensitivity reactions (HRs) and extracutaneous presentations associated with zoonotic sporotrichosis. A systematic review was performed, following the PRISMA guidelines to search for atypical/extracutaneous cases (mucosal, osteoarthritis, HRs, pulmonary, meningeal) of zoonotic sporotrichosis. A total of 791 published cases over 26 years (1998–2023) in eleven Brazilian states were reviewed. Most cases corresponded to a HR (47%; n = 370), followed by mucosal (32%; n = 256), multifocal (8%; n = 60), osteoarthritis (7%; n = 59), meningeal (4%; n = 32), and pulmonary (2%; n = 14) infections. When available (n = 607), the outcome was death in 7% (n = 43) of cases. Here, we show a frequent and worrisome scenario of zoonotic sporotrichosis in Brazil, with a high and dispersed incidence of atypical/extracutaneous cases throughout the Brazilian territory. Therefore, educational measures are necessary to make health professionals and the overall population aware of this fungal pathogen in Brazil as well as in other countries in the Americas. Full article

Background and Objectives: Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and lateral shifting of sphenoid mucosa as sphenoid mucosal flap (SMF) during the transsphenoidal exposure of the sella may be important for later closure. This is the first systematic review to evaluate the utility of sphenoid mucosal flap for sellar reconstruction after transsphenoidal surgery. Materials and Methods: A systematic literature search was performed in January 2023: Cochrane, EMBASE, PubMed, Scopus, and Web of Science. The following keywords and their combinations were used: “sphenoid mucosa”, “sphenoid sinus mucosa”, “sphenoid mucosal flap”, “sphenoid sinus mucosal flap”. From a total number of 749 records, 10 articles involving 1671 patients were included in our systematic review. Results: Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a vascularized pedicled flap or as a free flap. Three different types of mucosal flaps, an intersinus septal flap, a superiorly based flap and an inferiorly based flap, were described in the literature. Total SMF covering compared to partial or no SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks (p = 0.008) and a shorter duration of the postoperative lumbar drain (p = 0.003), if applied. Total or partial SMF resulted in fewer local complications (p = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation. Conclusions: SMF seems to be an effective technique for skull base reconstruction after transsphenoidal surgery, as it can reduce the usage of avascular grafts such as fat along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis and fungal infection, or it may improve the sinonasal quality of life by maintaining favorable wound healing through vascular flap and promote the normalization of the sphenoid sinus posterior wall. Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, particularly for higher-grade CSF leaks, are required. Full article