Search Results (146)

The human skin microbiota, a complex community of bacterial, fungal, and viral organisms, plays a crucial role in maintaining skin homeostasis and regulating host-pathogen interactions. Dysbiosis within this microbial ecosystem has been implicated in various dermatological conditions, including acne vulgaris, psoriasis, seborrheic dermatitis, and atopic dermatitis. This review, for the first time, provides recent advancements in all four layers of omic technologies—metagenomics, metatranscriptomics, metaproteomics, and metabolomics—offering comprehensive insights into microbial diversity, in the context of functional skin modeling. Thus, this review explores the application of these omic tools to in vitro skin models, providing an integrated framework for understanding the molecular mechanisms underlying skin–microbiota interactions in both healthy and pathological contexts. We highlight the importance of developing advanced in vitro skin models, including the integration of immune components and endothelial cells, to accurately replicate the cutaneous microenvironment. Moreover, we discuss the potential of these models to identify novel therapeutic targets, enabling the design of personalized treatments aimed at restoring microbial balance, reinforcing the skin barrier, and modulating inflammation. As the field progresses, the incorporation of multi-omic approaches into skin-microbiome research will be pivotal in unraveling the complex interactions between host and microbiota, ultimately advancing therapeutic strategies for skin-related diseases. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

Background/Objectives: Candidiasis, primarily caused by Candida albicans, and sporotrichosis, mainly caused by Sporothrix schenckii, are skin fungal infections that pose serious threats to global health. The Candida auris is a great concern in immunocompromised individuals, and while Sporothrix brasiliensis cause sporotrichosis, an infection commonly found in cats, this disease can be transmitted to humans through scratches or bites. Existing treatments for these fungal infections often cause problems related to resistance and significant side effects. Consequently, development of alternative therapeutic approaches such as nanotechnology-based topical lipid-based formulations is interesting. Thus, the objectives of this study were to prepare clove oil (CO)-in-water nanoemulsions (NEs) containing amphotericin B (AmB) and characterize them with respect to stability, release profile, and in vitro cytotoxic activity against Candida and Sporothrix strains. As a future alternative for the treatment of fungal skin diseases. Methods: Chemical analysis of clove oil was obtained by GC-MS. The NEs were produced using an ultrasound (sonicator) method with varying proportions of CO, Pluronic^® F-127, and AmB. The NEs were characterized by droplet size, morphology, stability and in vitro release profile. The antifungal and cytotoxic activity against C. albicans, C. auris, S. schenckii, and S. brasiliensis were ascertained employing agar diffusion and colorimetric MTT assay methods. A checkerboard assay was carried out using clove oil and amphotericin B against C. auris. Results: Eugenol was the major compound identified in CO at a concentration of 80.09%. AmB-loaded NEs exhibited particle sizes smaller than 50 nm and a polydispersity index below 0.25. The optimal Ne (NEMLB-05) remained stable after 150 days of storage at 4 °C. It exhibited rapid release within the first 24 h, followed by a slow and controlled release up to 96 h. NEMLB-05 more effectively inhibited C. auris compared to free AmB and also demonstrated greater activity against C. albicans, S. schenckii, and S. brasiliensis. Clove oil and amphotericin B presented synergism inhibiting the growth of C. auris. Conclusions: The selected CO-in-water NEs containing AmB demonstrated promising potential as a topical therapeutic alternative for treating fungal infections. Full article

Tinea incognito is an incorrectly diagnosed form of fungal infection due to a changed clinical picture as a result of systemic or topical corticosteroids or even local immunomodulators. This type of skin lesion is most often located on the trunk but can affect any part of the body. We present a case report of 76-year-old woman with a history of systemic lupus erythematosus who was admitted to hospital because of extensive, painful, and burning erythematous and papular lesions in an annular pattern, covered with a thick, yellow crust, located on the scalp and neck. The skin lesions were accompanied by extensive hair loss. The patient had previously undergone intensified treatment of the underlying disease due to the exacerbation of skin lesions of a subacute cutaneous lupus erythematosus type. A suspicion of tinea incognito was raised, and direct mycological examination and culture confirmed the presence of dermatophytes (Microsporum spp.). Tinea incognito can be difficult to diagnose because the clinical picture is relatively nonspecific and can mimic other dermatoses, such as subacute lupus erythematosus. Therefore, in doubtful cases it is necessary to perform a direct test and culture for fungal infection, especially before initiating treatment with glucocorticosteroids and other immunosuppressive agents. Full article

Dermatophytosis is a fungal infection that affects the skin, hair, and nails, impacting approximately 25% of the global population. Nannizzia gypsea is a geophilic fungus that can cause infections in humans and animals. Several studies have been conducted regarding its virulence, or ability to cause disease. This species may produce keratinolytic enzymes and form biofilms, which can increase resistance to treatment. Thus, this study focuses on investigating the biofilm formation of N. gypsea isolated from canine dermatophytosis using an ex vivo hair model, its biofilm extracellular matrix macromolecular contents, and the expression of genes involved in the colonization of keratinized surfaces. The biofilm was analyzed for metabolic activity using the XTT reduction assay, crystal violet staining to measure biofilm biomass, scanning electron microscopy (SEM), and the presence of polysaccharides, proteins, and extracellular DNA in the biofilm extracellular matrix. The virulence genes subtilisin 7, fungalysin (extracellular metalloproteinase), and efflux pump (Multidrug and Toxin Extrusion Protein 2) were evaluated by qPCR, comparing the planktonic and biofilm phenotypes. N. gypsea formed a robust biofilm, which matured after 5 days. Scanning electron microscopy (SEM) revealed the presence of an extensive extracellular matrix. In the hair model, the characteristic ectothrix parasitism of the species is observable. The gene expression analysis revealed a higher expression of all evaluated genes in the biofilm form compared to the planktonic form. Thus, N. gypsea exhibits a biofilm characterized by a robust extracellular matrix and high gene expression of factors related to pathogenesis and resistance. Full article

Background: This study investigates the cytotoxicity of microbial polyketides biosynthesized by Monascus species through both in silico and in vitro approaches. Methods: Six main know Monascus-derived polyketides were analysed in silico an an vitro. Results: In silico tests reveal that the main derived compounds exhibit lipophilic properties, indicating their potential suitability as active ingredients in dermato-cosmetic formulations. In silico tests revealed significant flexibility and high degrees of unsaturation for some Monascus-derived polyketides, suggesting a broad interaction potential and a propensity for chemical instability. In silico permeability tests indicated low epidermal penetration. Cytotoxicity assays conducted in vitro on a HaCaT cell line revealed varying levels of cytotoxicity among the three classes of fungal polyketides. Yellow polyketides derived from Monascus purpureus and Monascus ruber exhibited moderate cytotoxicity, while orange polyketides derived from the same strains showed low cytotoxicity. Red, orange, and yellow polyketides derived from a high-productive Monascus sp. genus showed low or negligible cytotoxicity. After 48 h of exposure, the cytotoxic profiles of all Monascus polyketides remained relatively stable. The IC₅₀ values obtained through linear or nonlinear models supplied by EXCEL MS Office or for the Systat programme indicated moderate-to-low cytotoxicity for polyketides derived from Monascus ruber and Monascus purpureus. The bioproducts derived from high-productive Monascus sp. exhibited weak or negligible cytotoxicity. Conclusions: The results obtained suggest that the Monascus-derived polyketides possess promising properties for therapeutic and cosmetic applications, but their chemical stability must be considered in the case of dermatological formulations. Full article

Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article

Background: Fungal infections pose an increasingly predominant threat to human and animal health. Modified compounds derived from chemo-diverse natural products offer enhanced therapeutic efficacies and promising approaches to combat life-threatening fungal pathogens. Methods: We performed biosynthetic gene clusters analysis of 2,4-diacetylchloroglucoside (DAPG) in 4292 shotgun metagenomes samples from the healthy and diseased skin. Then, we assessed the antifungal activity of DAPG and the derivative 2,4-diproylphloroglucinol (DPPG) against pathogenic fungi by minimum inhibitory concentrations. The inhibitory effects of DPPG were measured using hyphal growth assay and spore germination assay. Concurrently, the mechanism of DPPG on Aspergillus fumigatus was investigated in membrane permeability and fluidity. The therapeutic efficacy was evaluated in a Galleria mellonella infection model. Results: We observed a significantly higher abundance of bacteria harboring DAPG biosynthetic clusters on healthy skin compared to diseased skin. Further, we designed and synthesized a series of phloroglucinol derivatives based on DAPG and obtained an antifungal candidate DPPG. DPPG not only exhibited robust antifungal activity against Aspergillus spp. and Candida spp. but also impaired hyphal growth and spore germination of A. fumigatus in vitro. A mechanism study showed that DPPG reduced membrane fluidity and increased the leakage of cellular contents, resulting in membrane perturbation and fungal death. Lastly, the therapeutic efficacy of DPPG was confirmed in a G. mellonella infection model. Conclusions: Our study demonstrates that DPPG is a potent scaffold to combat invasive fungal infections. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, with interleukin (IL)-4, IL-13, and IL-31 recognized as key mediators. Prurigo nodularis (PN) is another chronic inflammatory disorder driven by T helper type 2-mediated inflammation and neural dysregulation, leading to severe pruritus. Nemolizumab, a humanized monoclonal antibody targeting IL-31 receptor A, has been approved for use in the treatment of AD and PN. Clinical trials have demonstrated significant reductions in pruritus and cutaneous symptoms associated with its use. In clinical practice, acute eczema and edematous erythema frequently occur, occasionally necessitating the discontinuation of treatment. Despite these observations, no comprehensive review has examined nemolizumab-associated cutaneous adverse events. This review aimed to examine various cutaneous reactions associated with nemolizumab therapy, including psoriasiform eruptions, AD exacerbation, bullous pemphigoid, drug-induced eruptions, and fungal infections. Potential mechanisms underlying these reactions include T-cell activation due to drug sensitization, immune responses triggered by nemolizumab acting as a hapten, and a relative increase in IL-4 and IL-13 levels following IL-31 inhibition. However, the precise pathophysiological mechanism and risk factors remain unclear, and standardized clinical management guidelines are lacking. Further accumulation of clinical data and immunological research are essential for developing evidence-based strategies to manage these adverse events, ensuring treatment continuity and optimizing patient outcomes. Full article

The study of the fungal communities of the skin constitutes a pivotal component of skin microbiome research. Within these communities, the genus Malassezia stands out as a major constituent, representing 50% to 80% of the total fungal colonization on the skin of healthy individuals. The excessive growth or metabolic irregularities of this genus are intimately connected with the onset of various skin disorders that are intrinsically linked to its lipid-dependent nature. Cutaneous lipid metabolism is indispensable for maintaining the skin barrier function and skin health. Malassezia possesses the ability to encode multiple lipase genes, and the secretion of these lipases plays a pivotal role in the survival strategies of the fungi. This review explores recent advances in the ecological niche of Malassezia in skin microecological homeostasis, its mechanism of disrupting skin lipids through catabolic metabolites, and the relationship between this disruption of the skin lipid barrier and skin diseases. This review offers a reference for future research on the mechanisms by which Malassezia affects lipid metabolism and provides a theoretical foundation for the development of innovative therapeutic approaches for dermatological conditions. Full article

The dynamic development of various branches of medicine and pharmacy, along with the emergence of new preventive and alternative therapies for various diseases, creates opportunities for new solutions utilizing carriers of active substances. Their therapeutic effect may occur through direct contact with skin lesions or indirectly, where medicinal substances penetrate the capillary network in the deeper layers of the skin and reach the bloodstream. The aim of the research was to obtain carriers with a matrix consisting of two renewable-source polymers (chitosan and ethylcellulose) and a core material derived from Ginkgo biloba green leaf extract (GBE). The obtained ethylcellulose microcapsules with encapsulated chitosan nanoparticles with extract {Et[Ch(GB)NP]} were characterized with respect to size, shape, surface morphology (SEM microscopy), and active substance release kinetics (UV-VIS and mathematical release models). The kinetics of active substance release were analyzed using UV-VIS spectroscopy and mathematical release models. The released active components were assessed microbiologically for activity against six bacterial strains and two fungal strains, as well as chromatographically using HPLC-ESI-QTOF-MS/MS fingerprinting. The microcapsules with a dual polymer layer exhibited a slow release of the core material, which demonstrated microbiological activity. The strongest antimicrobial effects were observed against Klebsiella pneumoniae and Salmonella enteritidis, with a minimum inhibitory concentration (MIC) of 410 µg/mL. The release of the core material from the double-layer polymer structures was more efficient in a physiological saline environment, with the best fit for the extract release kinetics following a zero-order model (regression coefficient R² = 0.9939). The obtained microcapsules with a dual polymer layer show great potential for therapeutic applications in the medical industry. Their controlled release properties and antibacterial effectiveness make them a promising carrier for active substances in modern therapies. Full article

Candidemia and invasive candidiasis represent critical healthcare-associated fungal infections that pose substantial challenges to medical systems worldwide. These conditions arise when fungi from the Candida genus infiltrate the bloodstream or deeper tissues, leading to a range of clinical manifestations. Among the various species, Candida albicans continues to hold its position as the most frequently encountered causative agent, largely due to its prevalence and adaptability within human hosts. However, it is far from the only significant player; other Candida species, such as Candida glabrata, Candida parapsilosis, and the particularly concerning Candida auris, contribute significantly to the disease burden and exhibit varying dominance depending on geographic regions. The clinical presentation of these infections can differ widely, spanning from subtle, almost imperceptible symptoms in some patients to severe, life-threatening fulminant sepsis in others, often accompanied by alarmingly high mortality rates that underscore the urgency of effective management strategies. Several well-established risk factors predispose individuals to developing invasive candidiasis and candidemia. Breaches in the body’s natural barriers—such as the skin (cutaneous) or the gastrointestinal (GI) tract—provide entry points for these opportunistic pathogens. Additionally, deficiencies in the host’s immune responses, whether due to medical treatments, underlying diseases, or genetic predispositions, heighten vulnerability to infection. Among the diverse Candida species, Candida auris has emerged as an especially troubling entity in recent years. This multidrug-resistant species is notorious for its resistance to standard antifungal therapies, which complicates treatment efforts and contributes to elevated morbidity and mortality rates. Its rapid global spread has positioned it as a formidable public health threat, prompting heightened surveillance and research into its behavior and control. Full article

Ophidiomyces ophidiicola, the fungus causing Snake Fungal Disease (SFD) or ophidiomycosis, is prevalent in North American snakes and can have deleterious population effects. Northern pine snakes (Pituophis melanoleucus melanoleucus) in New Jersey often test positive for ophidiomycosis. In this paper, we use qPCR to examine changes in prevalence from 2018 to 2023, and differences by age, sex, and morphological sampling locations. We swabbed ventral surfaces, head, and cloaca of snakes, and lesions and eyes if there were clinical ophidiomycosis signs. A snake was considered positive if any site was positive by qPCR. The prevalence was 47% (2018), increased to 100% (2022), but declined to 46% in 2023. The prevalence was highest in snakes with lesions (46–100%); head swabs had the lowest rates. The more lesions a snake had, the more likely it was that at least one would be positive. Males had significantly more lesions than females, but the prevalence was similar. In 2023, the prevalence of O. ophidiicola was low, but the prevalence of lesions did not decrease as markedly. We discuss the temporal changes in the positivity for O. ophidiicola and its implications for ophidiomycosis effects, suggesting that the fungus is endemic in this population. Full article

Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human populations. Here, we reviewed published reports (2009–2024) of dermatophyte infections in animals and in humans with a history of animal contact. A literature search was completed in October 2024 using PubMed, Embase (Ovid), and Web of Science (Core Collection), which identified 250 articles. Generally, dermatophytes tend to infect younger animals with long hair and exhibit a species-specific host range. Microsporum canis was the most commonly reported species—linked to cats—that can cause tinea capitis, especially concerning the development of kerion in children. Trichophyton verrucosum is strongly associated with cattle. The Trichophyton mentagrophytes complex shows a diverse range of animal hosts, with rabbits being most frequently reported; however, T. mentagrophytes var. erinacei is almost exclusively isolated from hedgehogs, and T. mentagrophytes var. benhamiae is more commonly found on rodents (e.g., guinea pigs). Lastly, the geophilic Nannizia gypsea has been isolated from both dogs and cats. Managing dermatophyte zoonoses is an ongoing challenge, as healthcare providers may empirically treat with corticosteroids or antibacterial agents due to its atypical inflammatory appearance. Evidence of in vitro resistance against griseofulvin and fluconazole has been documented in multiple zoonotic dermatophyte species. Resistance development against terbinafine and itraconazole is also a possibility, although the number of reports is scarce. Under the principles of the One Health approach, research on human fungal diseases should take animal and environmental factors into account. A renewed call for increased testing efforts is warranted. Full article