Search Results (185)

Cutaneous infections caused by dematiaceous fungi are rare in the general population but are increasingly recognized in solid organ transplant recipients as a consequence of prolonged immunosuppression. When Alternaria species are confirmed as the causative agents of a skin infection, the condition is referred to as alternariosis. These infections may clinically resemble bacterial or neoplastic lesions and require accurate diagnosis and individualized therapy. We report one case of cutaneous alternariosis in a kidney transplant recipient receiving tacrolimus-based immunosuppression. The patient was a 47-year-old woman who sustained minor trauma to her knee three months after transplantation. She developed an ulcerated, crusted lesion, which coincided with severe neutropenia. Histology, culture and molecular identification confirmed A. infectoria. Treatment included systemic azole therapy (voriconazole followed by isavuconazole) and surgical excision, resulting in resolution without recurrence. This case highlights the importance of early recognition of alternariosis in transplant recipients. Successful management typically requires combined surgical and systemic antifungal therapy, with careful monitoring of drug interactions and immunosuppressive levels to prevent toxicity or rejection. Full article

Superficial fungal skin infections are common but often misdiagnosed, which may result in inappropriate treatment and the worsening of symptoms. An accurate and timely diagnosis is essential to differentiate these infections from similar conditions such as secondary syphilis, annular psoriasis, and pityriasis rosea. This single-centre prospective cohort study at the National Skin Centre, Singapore, evaluated the diagnostic agreement between direct microscopy and fungal culture. Between August and December 2022, 268 skin scrape samples were collected from 149 patients with suspected fungal infections. Microscopy identified 67 (25.0%) positives, while fungal culture detected 42 (16.7%) positives. Among the 252 samples tested with both methods, 213 (84.5%) showed concordant results (κ = 0.487, p < 0.0001), a finding that indicates moderate agreement. The most commonly cultured organisms were Trichophyton rubrum and T. mentagrophytes. Our findings suggest that both microscopy and fungal culture may be performed to prevent true-positive cases from being missed. However, in cases where cost is a concern, microscopy can be selected as an initial diagnostic tool. Should microscopy be negative in cases with high clinical suspicion for fungal infection or when empirical treatment fails, culture remains a valuable follow-up test. These findings support a stepwise diagnostic approach—using microscopy first, then followed by culture when necessary—to improve diagnostic accuracy while enabling timely treatment. Full article

Obesity, a global health crisis, is linked to chronic low-grade inflammation and an increased risk of developing various chronic diseases, including psoriasis. Probiotics, postbiotics, and fermented foods have shown promise in combating inflammation and obesity. This study aimed to develop and characterize a chicory extract fermented with Bacteroides fragilis (C-B. fragilis) and its supernatant (phyto-postbiotic supernatant, PPS) as potential treatments for obesity, inflammation, and psoriasis. Polyphenols, organic acids, and amino acids were identified in the metabolic profile of C-B. fragilis. PPS and C-B. fragilis extract both revealed potent anti-inflammatory, anti-obesity, and antioxidant activities. In vitro assays highlighted that PPS significantly reduced the production of reactive oxygen species (ROS), the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) in macrophages, and the secretion of IL-1β in LPS-stimulated PBMCs. Moreover, PPS decreased triglyceride content in human adipocytes and modulated the expression of leptin and adiponectin. Regarding psoriasis, PPS reduced pro-inflammatory cytokines (IL-6, IL-1β) in both psoriatic keratinocytes and a co-culture model mimicking the skin-adipose tissue interface. In addition, PPS lowered S100 calcium-binding protein A7 (S100A7) expression in the co-culture model, suggesting a potential role in restoring skin barrier function. In summary, our results highlight the potential of PPS extract (supernatant of chicory fermentation by Bacteroides fragilis) as a promising therapeutic strategy for the management of obesity-related inflammation and psoriasis. Full article

Reliable methods for the isolation and culture of human eccrine sweat gland cells (SGCs) are essential for studying glandular biology and developing tissue-engineered skin substitutes (TESs) that restore full skin function. However, maintaining the glandular phenotype of SGCs in vitro remains a major challenge. In this study, we present an optimized isolation protocol combining enzymatic digestion with mechanical separation to improve SGC yield and purity, while also enabling keratinocyte isolation from a single human skin biopsy. We then evaluated two culture strategies, 2D monolayers and 3D spheroids, to determine their impact on SGC identity and proliferation. While 2D culture supported cell expansion, SGCs and keratinocytes exhibited highly similar marker expression profiles, with the absence of functional SGC markers (AQP5, α-SMA) reflecting a shift toward less differentiated phenotypes. In contrast, SGCs cultured in 3D spheroids preserved the expression of SGC-specific markers (AQP5, K18, α-SMA), distinguishing them from keratinocytes; however, their growth and structural organization were suboptimal under these 3D conditions. Moreover, SGCs expanded in 2D did not regain their glandular features when reintroduced into 3D culture, suggesting potential limitations in phenotype recovery. These results highlight the need for improved culture systems that maintain SGC identity while supporting expansion. Advancing such methods is a critical step toward integrating functional sweat glands into TESs and achieving complete skin regeneration for clinical applications. Full article

Interleukin (IL)-15 is primarily known as a pro-inflammatory and anti-apoptotic cytokine, which stimulates the proliferation and survival of key immunocytes, including macrophages (MACs). Yet, it remains unclear how IL-15 specifically impacts MACs in intact human skin, particularly immunoinhibitory, IL-10-producing/secreting M2 MACs (CD206⁺IL-10⁺). In the current pilot study, we explored this in organ-cultured healthy human eyelid skin in the presence of IFNγ (100 IU/mL) to mimic a pro-inflammatory signaling milieu found in several chronic immunodermatoses. Quantitative immunohistomorphometry showed that IFNγ significantly reduced the number of CD68⁺MACs, M2 CD206⁺MACs, and immunoinhibitory CD206⁺IL-10⁺MACs. Moreover, co-administering recombinant human (rh) IL-15 after inducing inflammation by IFNγ largely reversed the IFNγ-induced decline in MAC populations. To investigate if this was mediated via the private IL-15 receptor alpha (IL-15Rα), we successfully silenced IL-15Rα in human skin ex vivo. Indeed, co-administration of IL-15Rα siRNA abrogated the rhIL-15 protection of M2 CD206⁺MACs against IFNγ, but not of the CD206⁺IL-10⁺MAC subpopulation. These pilot data suggest that IL-15 maintains immunoinhibitory M2 CD206⁺IL-10⁺MACs in human skin under IFNγ-dominated inflammatory conditions. Therefore, it deserves to be explored whether IL-15 or IL-15Rα agonists can exert therapeutic benefit in chronic inflammatory dermatoses by preserving the intracutaneous pool of anti-inflammatory dermal M2 MACs. Full article

Blastomycosis, caused by dimorphic fungi of the Blastomyces genus, is endemic to regions in North America, including the Great Lakes and other parts of Canada and the United States of America. The infection primarily occurs through the inhalation of airborne conidia from contaminated soil and decaying organic matter. Pulmonary involvement is most common, but dissemination to other organs such as the skin and bones can occur, especially in immunocompromised individuals. Diagnosis is challenging due to its clinical overlap with other diseases. Culture remains the gold-standard diagnostic method, but is time-consuming, with sensitivity ranging from 66.4% to 86%. Tissue histopathology offers quicker results but has sensitivities ranging from 36% to 85%. Antigen detection assays show high sensitivity from 76.3% to 91.3% but suffer from cross-reactivity with other fungi. PCR methods offer high specificity, with sensitivity ranging from 67.6% to 100%. In immunocompromised patients, blastomycosis is often more severe, with a mortality rate exceeding 30%. Multi-modal diagnostic approaches are crucial for accurate detection and management. Full article

Schaalia canis is a Gram-positive, facultatively anaerobic, rod-shaped bacterium originally isolated from the mucosa and skin of dogs. While it is a part of the normal canine oral flora, it has rarely been implicated in human disease, with only one prior case of cellulitis reported following a dog bite. Case Presentation: We present the case of a 57-year-old immunocompetent man who developed osteomyelitis of the left index finger following a delayed presentation after a dog bite. Despite initial conservative management with empirical oral antibiotics, the infection progressed, eventually requiring surgical debridement and the terminalisation of the finger at the proximal interphalangeal joint. Cultures from intraoperative bone specimens yielded the growth of Schaalia canis, with no other pathogenic organisms identified on the extended culture. Conclusions: This is the first documented case of Schaalia canis-associated osteomyelitis in a human and the first to necessitate a surgical intervention, expanding the known clinical spectrum of this organism. This case underscores the risks of delayed intervention in polymicrobial animal bite wounds and highlights the emerging role of Schaalia species as opportunistic zoonotic pathogens, particularly in the setting of deep, refractory infections. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Systemic sclerosis (SSc) is an autoimmune fibrotic disorder affecting the skin and internal organs, categorized as either limited cutaneous SSc, where distal areas of skin are involved, or diffuse cutaneous SSc, where more extensive proximal skin involvement is seen. Vascular remodelling and internal organ involvement are frequent complications in both subsets. Multiple pathogenic mechanisms have been demonstrated, including production of disease-specific autoantibodies, endothelial cell damage at an early stage, infiltration of involved tissues by immune cells, as well as environmental factors triggering the onset such as solvents and viruses. Although not strongly familial, susceptibility to SSc is associated with multiple single nucleotide polymorphisms in immunoregulatory genes relevant to antigen presentation, T cell signalling and adaptive immunity, as well as innate immunity. In addition, several lines of evidence demonstrate abnormalities within the epithelial cell layer in SSc. Macroscopically, the SSc epidermis is pigmented, thickened and stiff and strongly promotes myofibroblasts in co-culture. Moreover, multiple activating factors and pathways have been implicated in the disease epidermis, including wound healing responses, induction of damage associated molecular patterns (DAMPS) and the release of pro-fibrotic growth factors and cytokines. Similar to SSc, data from studies of cutaneous wound healing indicate a major role for epidermal keratinocytes in regulating local fibroblast responses during repair of the wound defect. Since the epithelium is strongly exposed to environmental factors and richly populated with protective immune cells, it is possible that disease-initiating mechanisms in SSc involve dysregulated immunity and tissue repair within this cell layer. Treatments designed to restore epithelial homeostasis or else disrupt epithelial–fibroblast cross-talk could be of benefit in this severe and resistant disease. Accordingly, single cell analysis has confirmed an active signature in SSc keratinocytes, which was partially reversed following a period of JAK inhibitor therapy. Full article

Melanoma is the most common type of skin cancer. Melanomas are well known for their ability to metastasize to other organs, including the lungs, liver, brain, and bones. The ability of melanoma cells to switch among different phenotypes is a key mechanism that underscores their metastatic potential. The objective of this work is to report here on the effect of calcium sulfide (CaS) dispersions in melanoma cells. Melanomas with the epithelial- and mesenchymal-like phenotypes were observed during cell culture preparation. The dose-dependent viability was explored up to slightly less than 3% per volume of cell culture. The dispersion reduced the relative percentage of melanomas with the epithelial- and mesenchymal-like phenotypes to (57 ± 5) and (55 ± 5)%, respectively, at 24 h post treatment. In contrast, the viability of normal fibroblasts treated with the dispersion or melanoma cells treated with the reactants used to prepare the dispersion remained nearly constant, with a value range of (100.0 ± 0.2)% for the control and (97 ± 4)% and (93 ± 2)% for doses as high as 2 and 3% per volume of cell culture, respectively. Fluorescence imaging measurements were consistent with the release of cytochrome c from the mitochondria and its translocation to the cell nuclei. The average expression of caspases 3 and 9 was found to be 3 and 1.4 times higher than in the corresponding melanoma control, respectively, which was consistent with intrinsic apoptosis. The response of vinculin expression was slightly different in both cell phenotypes. Vinculin was found to delocalize in the cytoplasm of treated mesenchymal melanoma cells, with a slightly higher concentration at the end of the actin fibers. A statistically significant increase (p < 0.0001) in the number of focal adhesion points (FAP) at the edge of the cell membrane–external cellular matrix (ECM) interphase was observed in post-treated melanoma that exhibited the epithelial-like phenotype. The changes in vinculin expression and FAP and the reduced viability of the melanomas were consistent with regulation of proteins associated with programmed cell death. It is thus proposed that the sulfides produced from the reactions of the nanoclusters in the acidic environment facilitate the regulation of proteins required to initiate apoptosis, although other processes may also be involved. We conclude that CaS may be an adequate chemical to selectively reduce melanoma viability with little effect on benign fibroblasts. Full article

Hyaluronic acid (HA) is an unbranched polysaccharide particularly abundant in the extracellular matrix (ECM) of soft connective tissues. In humans, about 50% of the total HA in the organism is localized in the skin. HA plays an essential role in the hydration of the ECM, in the regulation of tissue homeostasis, in the resistance to mechanical stimuli/forces, and in the modulation of tissue regeneration. For these reasons, HA is widely used in regenerative medicine and cosmetics. In this study we used an innovative fluid dynamic system to investigate the effects of a cross-linked macrostructural HA formulation on dermal collagen of healthy human skin explants. The good preservation of skin explants provided by the bioreactor allowed applying refined high-resolution microscopy techniques to analyze in situ the HA-induced modifications on the ECM collagen fibrils up to 48 h from the application on the skin surface. Results demonstrated that this HA formulation, commercially proposed for subcutaneous injection, may act on dermal ECM also when applied transcutaneously, improving ECM hydration and modifying the organization of the collagen fibrils. These findings, obtained by the original combination of explanted human skin use with an advanced culture system and multiscale imaging techniques, are consistent with the volumizing and anti-aging effect of HA. Full article

Research on fish skin artefacts’ dyeing practices among the Nivkh, Nanai, Ulchi, Udegei, Oroch, and Negidal Indigenous Peoples of the Amur River basin remains scarce. These fishing communities traditionally crafted fish skin garments, essential to their subsistence and spiritual life, adorning them with protective motifs. While artistic and cultural aspects of these belongings have been explored, their dyeing techniques remain understudied. This multidisciplinary research examines natural colourants in fish skin artefacts from international museum collections, using historical textual research, ethnographic records, Native Traditional Knowledge, and previous dye analysis by museum conservators. Findings reveal a restricted but meaningful palette of red, blue, yellow, and black colourants, sourced from plants, minerals, and organic materials. Early dyers extracted blue from indigotin-rich plants such as Polygonum tinctorium, or from Commelina communis petals. Red hues were obtained from Carthamus tinctorius petals, introduced through Silk Route trade networks, or from minerals like red ochre. Black was derived from carbon black, while riverine minerals were ground with dry fish roe diluted with water to create additional colour variations. This study first reviews fish skin use in Amur River Indigenous cultures, explores nineteenth-century dyeing materials and techniques, and finally considers broader implications for Indigenous material heritage. Full article

Background: Fluoroquinolones, available in topical and oral formulations, are used to manage bacterial skin and soft tissue infections, including Pseudomonas aeruginosa, atypical mycobacteria, and select multidrug-resistant Gram-negative organisms. Their excellent tissue penetration, bactericidal activity, and convenient dosing make them effective for certain skin and soft tissue infections. However, their use is limited by potential safety concerns, including tendinopathy (odds ratio up to 9.1 in corticosteroid users), QT interval prolongation with risk of torsades de pointes, phototoxicity, and rising antimicrobial resistance. Methods: A literature search of PubMed, Scopus, and Web of Science was conducted for articles from January 1985 to April 2025 with the search terms (quinolone OR fluoroquinolone) AND (dermatology OR “skin and soft tissue infection” OR “skin structure infection”). Abstracts and presentations were excluded. A Google search used the same terms for articles from government regulatory agencies. Results: This review provides practical guidance on the clinical use of topical and oral fluoroquinolones in dermatology. Delafloxacin demonstrated over 90% cure rates in trials for complicated skin infections. However, serious safety concerns remain, including a ninefold increase in tendinopathy risk among older adults on corticosteroids and corrected QT intervals exceeding 500 milliseconds in high-risk patients. Phototoxicity varies, with agents like sparfloxacin linked to heightened ultraviolet sensitivity. Resistance to ciprofloxacin exceeds 20 percent in Escherichia coli and P. aeruginosa in some populations. Culture-based prescribing, shorter treatment courses, and preference for topical treatments can reduce risk and preserve efficacy. Conclusions: Fluoroquinolones remain clinically useful in dermatology when prescribed selectively. Their appropriate use requires careful attention to patient risk factors along with their evolving resistance patterns and ongoing stewardship efforts. Full article

The development of alternatives to animal models and traditional cell cultures has led to the emergence of organ-on-chip (OoC) systems, which replicate organ functions under both physiological and pathological conditions. These microfluidic platforms simulate key tissue interfaces—such as tissue–air, tissue–liquid, and tissue–tissue interactions—while incorporating biomechanical stimuli to closely resemble in vivo environments. This makes OoC systems particularly suitable for modeling biological barriers such as the skin, the placenta, and the blood–brain barrier, which play essential roles in maintaining homeostasis. This review explores various biological barrier models that can be replicated using the OoC technology, discussing the integration of induced pluripotent stem cells (iPSCs) to advance personalized medicine. Additionally, we examine the methods for assessing barrier formation, including real-time monitoring through integrated sensors, and discuss the advantages and challenges associated with these technologies. The potential of OoC systems in disease modeling, drug discovery, and personalized therapeutic strategies is also highlighted. Full article

Androgenetic alopecia is associated with testosterone-mediated anagen-to-catagen transition and matrix keratinocyte apoptosis in hair follicle cells. Activation of Nox isozymes is involved in testosterone-mediated keratinocyte apoptosis, leading to androgenetic alopecia. This indicates that Nox isozymes can serve as therapeutic targets for androgenetic alopecia. The isolated compounds from natural products were screened to evaluate their ROS-inhibition efficacy and it was found that 1′S-1′-acetoxychavicol acetate (ACA, 26), a natural compound isolated from Alpinia galanga (L.) Willd. (Zingiberaceae), exhibits inhibitory activity on Nox isozymes. Nox inhibition by ACA suppressed testosterone-dependent H₂O₂ generation and cell death in keratinocytes. Incubation with ACA in human hair follicle organ culture mitigated testosterone-dependent suppression of hair growth. We validated that ACA regulates androgenetic alopecia in a mouse model. Local application of ACA on the dorsal skin in an androgenetic alopecia model of C57BL/6 mice significantly suppressed testosterone-induced hair loss in a dose-dependent manner. Moreover, hair follicle length in ACA-treated mice was enhanced compared to that in control mice. These findings provide a molecular mechanism in which ACA inhibits Nox activity in hair follicle cells, indicating its potential as an effective treatment of AGA. Full article