Search Results (177)

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

Skin ageing is a complex biological process influenced by cellular senescence, oxidative stress, and extracellular matrix degradation. Emerging evidence suggests that plant-derived bioactive compounds and extracellular vesicles (EVs) play a crucial role in modulating cellular homeostasis, promoting tissue regeneration, and counteracting age-related morphological and functional changes. This study investigates the impact of Haberlea rhodopensis in vitro culture extracts, native and enriched with EVs, on key cellular processes, including morphology, mitochondrial dynamics, lysosomal activity, gene expression, and genotoxicity in human dermal fibroblasts. The extracellular vesicles were identified in terms of shape, size, and morphology using dynamic light scattering, negative staining and observation under a transmission electron microscope. A comprehensive in vitro analysis was conducted utilizing light microscopy to assess cellular morphology and lysosomal mass, fluorescence microscopy for actin cytoskeletal organization, mitochondrial integrity, and nuclear morphology, and gene expression profiling for markers associated with collagen synthesis (COL1A1, COL3A1), senescence (CDKN1A), and oxidative stress response (NFE2L2). Additionally, cell cycle progression was evaluated, and genotoxicity was assessed using the neutral comet assay. Haberlea rhodopensis in vitro culture extracts and EVs were found to preserve fibroblast morphology, enhance mitochondrial mass, and upregulate collagen-related gene expression. These effects were concentration-dependent. The extracts exhibited biocompatibility with minimal genotoxic effects, indicating their potential as safe bioactive agents for skin rejuvenation. The findings suggest that Haberlea rhodopensis in vitro culture extracts and their enrichment with extracellular vesicles hold promise for cosmetic and dermatological applications, particularly in enhancing collagen production, preserving cellular integrity, and mitigating age-related alterations in skin fibroblasts. Further studies are warranted to elucidate the underlying molecular mechanisms and optimize formulation strategies for clinical translation. Full article

Advanced glycation end-products (AGEs) cause blood vessel damage and induce diabetic complications in various organs, such as the eyes, kidneys, nerves, and skin. As glycation stress causes aesthetic, physical, and functional changes in the skin, glycation-targeting skin anti-aging strategies are attracting attention in cosmetology and dermatology. The primary goal of this review is to understand the significance of glycation-induced skin aging and to examine the therapeutic potential of glycation-targeting strategies. This study covers experimental and clinical studies exploring various interventions to attenuate glycation-induced skin aging. Glycation stress decreases the viability of cells in culture media, the cell-mediated contraction of collagen lattices in reconstructed skin models, and the expression of fibrillin-1 at the dermo-epidermal junction in the skin explants. It also increases cross-links in tail tendon collagen in animals, prolonging its breakdown time. However, these changes are attenuated by several synthetic and natural agents. Animal and clinical studies have shown that dietary or topical administration of agents with antiglycation or antioxidant activity can attenuate changes in AGE levels (measured by skin autofluorescence) and skin aging parameters (e.g., skin color, wrinkles, elasticity, hydration, dermal density) induced by chronological aging, diabetes, high-carbohydrate diets, ultraviolet radiation, or oxidative stress. Therefore, the accumulating experimental and clinical evidence supports that dietary supplements or topical formulations containing one or more synthetic and natural antiglycation agents may help mitigate skin aging induced by AGEs. Full article

Intra-abdominal and gastrointestinal mucormycosis are less frequent than rhino-orbito-cerebral and pulmonary mucormycosis, but highly lethal. Their diagnosis remains challenging due to the non-specific clinical presentation. We collected English-language cases of intra-abdominal and gastrointestinal mucormycosis in non-haematological and non-neonatal patients published up to October 2024. This review analysed the epidemiological, clinical, and therapeutic charts of 290 cases. A proportion of 53.4% were reported from India and the USA. The main predisposing conditions were diabetes, solid organ transplant, ICU, and corticosteroid treatment. The most common site was the stomach (53.8%). Gastrointestinal perforation, skin breakdown, and abdominal wall infection were sources of intra-abdominal localisation. The most common symptoms were abdominal pain, vomiting, and gastrointestinal bleeding. The diagnosis relied on histology (93.8%), mycology with microscopy and culture (38.8%), and molecular methods (9.9%). Mortality (52.9%) was lower when treatment was intravenous amphotericin B, combined or not with surgery. Prompt treatment, essential for a favourable outcome, relies on early suspicion and diagnosis. Gastrointestinal and intra-abdominal mucormycosis should also be suspected in patients admitted in ICU with ventilation/nasogastric tube and corticosteroids and those with abdominal trauma or surgery, presenting abdominal distension, pain, and GI bleeding. Mycological diagnosis including direct examination, culture and Mucorales qPCR on tissue should assist with rapid diagnosis and thus treatment. Full article

Background: Skin aging is a complex biological process affected by internal and external factors that disrupt the skin structure, especially in sun-exposed areas. Elastin and collagen in the dermis layer, responsible for the skin’s resistance and elasticity, have been the main subject of research. Since tyrosinase (TYR) is an enzyme found in different organisms and plays an essential role in melanogenesis, inhibitors of this enzyme have been the target mechanism for skin-bleaching product research. Methods: We selected the plant species Cotinus coggygria Scop., Garcinia mangostana L., Pistacia vera L., Vitis vinifera L., and propolis, which exhibited activity against a minimum of three target enzymes—elastase, collagenase, and TYR—in our previous screening study to find the suitable raw material for a cosmetic product. In the current research, the extracts from these samples were tested through a cell-free enzyme assay using validated elastase, collagenase, and TYR inhibition kits. We also performed the safety and efficacy tests of the selected extracts with 2D/3D cell culture methods. Results: Our data revealed the propolis extract among the tested ones displayed remarkable anti-inflammatory activity in the 2D (NF-κB induction: 10.81%) and 3D assays. Cotinus coggygria leaf and Garcinia mangostana shell extracts exhibited anti-inflammatory activity in the 2D luciferase reporter assay via TNFα addition. C. coggygria leaf, V. vinifera (grape) seed, and propolis extracts were selected for testing in 3D cell culture methods based on the 2D cytotoxicity results with cell viability values of 54.75%, 93.19%, and 98.64% at 34.25 µg/mL, respectively. The general phytochemical profiles of these three extracts were examined in terms of 53 phenolic compounds with LC-MS/MS, revealing that quinic acid, epicatechin, and acacetin were the dominant phenolics among the tested ones. Conclusions: It is the first study conducted to evaluate the use of the extracts indicated above in cosmetics by employing procedures involving 3D cell culture. Full article

We have previously demonstrated that receptor-interacting serine threonine kinase 1 (RIPK1) is expressed in hair follicles and regulates the hair cycle. In a mouse model, RIPK1 inhibitors also accelerated the telogen-to-anagen transition and elongated the anagen period. Here, we first investigated the involvement of RIPK1 in alopecia areata (AA). The mRNA and protein expression of RIPK1 was increased in the skin of an AA mouse model. Single-cell RNA sequencing and immunohistochemistry showed that RIPK1 was highly increased in dendritic cells (DCs) and CD8⁺ T cells. RIPK1 inhibitors (i.e., Necrostatin-1s and GSK2982772) delayed the onset of AA in the mouse model and reduced the numbers of DCs and CD8⁺ T cells in AA skin. The RIPK1 inhibitors also increased the hair length in a mouse hair organ culture mimicking AA. Collectively, these results suggest that RIPK1 is involved in AA onset via modulating immune cells, and RIPK1 inhibitors could prevent AA onset. Full article

Telocytes (TCs) are distinctive cells widely localized in the stromal compartment of several human organs, including the skin. By means of their peculiar prolongations named telopodes, skin TCs are organized in networks interconnected with a variety of adjacent cells, being thus supposed to take part in skin homeostasis through both cell-to-cell contacts and the release of extracellular vesicles. A disarrangement/loss of the TC network was shown in human fibrotic skin as well as in the murine model of bleomycin-induced cutaneous fibrosis, but whether such TC alterations may represent just a consequence or a trigger of the fibrotic process still remains to be clarified. Thus, we investigated the effects of skin TC secretome as conditioned medium (TC-CM) on the transition of skin fibroblasts into myofibroblasts promoted by the master profibrotic cytokine transforming growth factor β1 (TGFβ1). Primary cultures of both adult human skin TCs and fibroblasts were obtained by means of immunomagnetic cell separation. Nanoparticle tracking analysis was carried out to measure extracellular vesicles in TC-CM. The combination of multiple morphological, gene/protein expression, and functional assessments demonstrated that TC-CM was able to significantly prevent TGFβ1-induced fibroblast-to-myofibroblast transition. TC-CM did not influence cell viability, while it effectively inhibited TGFβ1-induced fibroblast proliferation, migration, and morphological changes. Indeed, TC-CM was able to reduce TGFβ1-mediated skin fibroblast phenotypic and functional differentiation into myofibroblasts, as shown by a significant decrease in FAP, ACTA2, COL1A1, COL1A2, FN1, and CTGF gene expression, α-smooth muscle actin, N-cadherin, COL1A1, and FN-EDA protein levels, and collagen gel matrix contraction. Furthermore, TC-CM significantly lowered TGFβ1-mediated ERK1/2 signaling pathway activation. This in vitro study proves for the first time that TCs may play an important role in skin homeostasis through the prevention of fibroblast-to-myofibroblast transition via paracrine mechanisms and affords the necessary basis to investigate in the future the feasibility of TC secretome as an innovative antifibrotic therapeutic tool. Full article