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Search Results (1,139)

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6 pages, 406 KiB  
Brief Report
One-Shot, One Opportunity: Retrospective Observational Study on Long-Acting Antibiotics for SSTIs in the Emergency Room—A Real-Life Experience
by Giacomo Ciusa, Giuseppe Pipitone, Alessandro Mancuso, Stefano Agrenzano, Claudia Imburgia, Agostino Massimo Geraci, Alberto D’Alcamo, Luisa Moscarelli, Antonio Cascio and Chiara Iaria
Pathogens 2025, 14(8), 781; https://doi.org/10.3390/pathogens14080781 - 6 Aug 2025
Abstract
Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus [...] Read more.
Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article
25 pages, 1504 KiB  
Article
Systemic Sclerosis with Interstitial Lung Disease: Identification of Novel Immunogenetic Markers and Ethnic Specificity in Kazakh Patients
by Lina Zaripova, Abay Baigenzhin, Zhanar Zarkumova, Zhanna Zhabakova, Alyona Boltanova, Maxim Solomadin and Alexey Pak
Epidemiologia 2025, 6(3), 41; https://doi.org/10.3390/epidemiologia6030041 - 6 Aug 2025
Abstract
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: [...] Read more.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article
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17 pages, 2085 KiB  
Article
Multifunctional Dermatological Effects of Whole-Plant Bassia scoparia Extract: Skin Repair and Protection
by Seogyun Jeong, Hye-Been Kim, Dong-Geol Lee, Eunjin Park, Seoyeon Kyung, Seunghyun Kang, Dayeon Roo, Sang Hyun Moh, Sung Joo Jang, Jihyeon Jang, HyungWoo Jo and Sanghun Lee
Curr. Issues Mol. Biol. 2025, 47(8), 617; https://doi.org/10.3390/cimb47080617 - 4 Aug 2025
Abstract
Bassia scoparia (Syn. Kochia scoparia (L.) Schrad.) is a medicinal plant whose fruit, Kochiae Fructus, has been extensively studied for its dermatological applications. This study focused on extracts from the whole plant B. scoparia (WPBS), excluding fruits, to address the research gap [...] Read more.
Bassia scoparia (Syn. Kochia scoparia (L.) Schrad.) is a medicinal plant whose fruit, Kochiae Fructus, has been extensively studied for its dermatological applications. This study focused on extracts from the whole plant B. scoparia (WPBS), excluding fruits, to address the research gap regarding the medicinal properties of non-fruit parts. The diverse skin benefits of WPBS, including its anti-photoaging, moisturizing, wound healing, anti-inflammatory, and anti-angiogenic effects, were investigated. The WPBS extract enhanced the viability of keratinocytes (HaCaT) without inducing cytotoxic effects. WPBS significantly reduced matrix metalloproteinase-1 (MMP-1) levels and increased collagen type I alpha 1 (COL1A1) levels (p < 0.01) in fibroblasts exposed to ultraviolet B (UVB) radiation, indicating strong anti-photoaging effects. WPBS upregulated skin hydration markers such as aquaporin-3 (AQP3) and hyaluronan synthase-3 (HAS3) and effectively accelerated fibroblast wound closure compared to the positive control. Furthermore, WPBS substantially downregulated the expression of inflammatory (COX-2 and IL-1β) and angiogenic markers (VEGF). Transcriptome analysis (RNA-seq) confirmed that WPBS suppressed inflammation-related and UV-induced gene expression pathways. Overall, these findings expand the therapeutic scope of B. scoparia beyond its traditional fruit use and suggest that WPBS is a promising botanical ingredient for various skin applications. Full article
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17 pages, 1768 KiB  
Article
Quality Status and Skin-Related Functional Properties of Traditional Korean Fermented Vinegars
by Hwan Hee Yu, So-Won Jang, Eungyeong Kim, Jong-Chan Kim and Mi Jang
Foods 2025, 14(15), 2728; https://doi.org/10.3390/foods14152728 - 4 Aug 2025
Abstract
The correlation between fermented vinegar’s physicochemical properties and functional characteristics, particularly skin-related functionalities, remains unclear. We analyzed the quality of widely consumed Korean fermented vinegars, including grain and persimmon vinegars, and their correlation with skin-related functionalities to establish quality control criteria linked to [...] Read more.
The correlation between fermented vinegar’s physicochemical properties and functional characteristics, particularly skin-related functionalities, remains unclear. We analyzed the quality of widely consumed Korean fermented vinegars, including grain and persimmon vinegars, and their correlation with skin-related functionalities to establish quality control criteria linked to functional properties. Fifteen traditional Korean grain vinegars and fourteen persimmon vinegars were collected; distilled white vinegar was used as the control group. Grain vinegars showed 3.57–100.00% collagenase and 62.38–77.03% tyrosinase inhibition; persimmon vinegars showed 0.00–94.50% and 30.75–71.54%, respectively. To determine which quality characteristics are high in fermented vinegar with high skin-related functionality, a correlation analysis was conducted. In grain vinegar, total nitrogen and free amino acids were strongly associated with skin-related functionalities. In persimmon vinegar, organic acids, particularly lactic acid, were correlated with skin-related effects; thus, both demonstrated the importance of quality assessment. Insights into relationships between the composition and functional properties of fermented vinegar were gained. Specific quality markers for managing skin-related functionality of Korean fermented vinegar established a scientific basis for standardizing quality control, developing high-value functional vinegar products, and ensuring consistent product quality. Full article
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14 pages, 4233 KiB  
Article
Immunological Markers Associated with Skin Manifestations of EGPA
by Silvia Brunetto, Federica Buta, Sebastiano Gangemi and Luisa Ricciardi
Int. J. Mol. Sci. 2025, 26(15), 7472; https://doi.org/10.3390/ijms26157472 - 2 Aug 2025
Viewed by 218
Abstract
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic [...] Read more.
Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article
(This article belongs to the Special Issue Skin, Autoimmunity and Inflammation 2.0)
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28 pages, 13735 KiB  
Article
Immunohistopathological Analysis of Spongiosis Formation in Atopic Dermatitis Compared with Other Skin Diseases
by Ryoji Tanei and Yasuko Hasegawa
Dermatopathology 2025, 12(3), 23; https://doi.org/10.3390/dermatopathology12030023 - 1 Aug 2025
Viewed by 260
Abstract
Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis [...] Read more.
Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions. Full article
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18 pages, 4624 KiB  
Article
Andrographis paniculata Extract Supports Skin Homeostasis by Enhancing Epidermal Stem Cell Function and Reinforcing Their Extracellular Niche
by Roberta Lotti, Laetitia Cattuzzato, Xuefeng Huang, David Garandeau, Elisabetta Palazzo, Marika Quadri, Cécile Delluc, Eddy Magdeleine, Xiaojing Li, Mathilde Frechet and Alessandra Marconi
Cells 2025, 14(15), 1176; https://doi.org/10.3390/cells14151176 - 30 Jul 2025
Viewed by 424
Abstract
Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human [...] Read more.
Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human skin. Using human skin explants and cell culture models, we demonstrated that APE treatment enhances DEJ composition by increasing Collagen IV and Laminin production while decreasing MMP-9 expression, without altering epidermal structure or differentiation. In the same model, APE preserved stemness potential by upregulating markers related to niche components (collagen XVII and β1-integrin), proliferation (Ki-67 and KRT15), and stem cell capacity (Survivin and LRIG1). In vitro studies revealed that APE selectively stimulated KSC proliferation without affecting transit amplifying cells and promoted Collagen IV and Laminin secretion, particularly in KSCs. Furthermore, in a co-culture model simulating a compromised DEJ (UVB-induced), APE increased Laminin production in KSCs, suggesting a protective effect against photo-damage. These findings indicate that APE enhances DEJ composition and preserves stem cell potential, highlighting its promise as a candidate for skin anti-aging strategies targeting stem cell maintenance and extracellular matrix stability to promote skin regeneration and repair. Full article
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17 pages, 4113 KiB  
Article
Protective Effect of Camellia japonica Extract on 2,4-Dinitrochlorobenzene (DNCB)-Induced Atopic Dermatitis in an SKH-1 Mouse Model
by Chaodeng Mo, Md. Habibur Rahman, Thu Thao Pham, Cheol-Su Kim, Johny Bajgai and Kyu-Jae Lee
Int. J. Mol. Sci. 2025, 26(15), 7286; https://doi.org/10.3390/ijms26157286 - 28 Jul 2025
Viewed by 284
Abstract
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application [...] Read more.
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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17 pages, 451 KiB  
Article
Primary and Recurrent Erysipelas—Epidemiological Patterns in a Single-Centre Retrospective Analysis
by Marta Matych, Agata Ciosek, Karol Miler, Marcin Noweta, Karolina Brzezińska, Małgorzata Sarzała, Joanna Narbutt and Aleksandra Lesiak
J. Clin. Med. 2025, 14(15), 5299; https://doi.org/10.3390/jcm14155299 - 27 Jul 2025
Viewed by 378
Abstract
Background/Objectives: Erysipelas is an acute bacterial skin infection, particularly affecting the lower limbs, with a tendency to recur. Despite its clinical importance, data on demographic and epidemiological risk factors, as well as factors influencing hospitalization, remain limited. This study aimed to analyze the [...] Read more.
Background/Objectives: Erysipelas is an acute bacterial skin infection, particularly affecting the lower limbs, with a tendency to recur. Despite its clinical importance, data on demographic and epidemiological risk factors, as well as factors influencing hospitalization, remain limited. This study aimed to analyze the epidemiological and clinical characteristics of patients hospitalized with primary and recurrent erysipelas, focusing on risk factors contributing to disease onset, recurrence, and prolonged hospitalization. Methods: A retrospective single-center analysis was conducted on 239 patients hospitalized for erysipelas at the Department of Dermatology, Pediatric Dermatology, and Oncology at the Medical University of Lodz. Data collected included demographics, lesion location, laboratory markers, comorbidities, and hospitalization outcomes. Statistical analyses were performed to assess associations between risk factors, disease recurrence, and hospitalization duration. Results: The majority of erysipelas cases (85.4%) involved the lower limbs, with a higher prevalence in men. Upper extremities were mostly affected in women, especially those who had undergone breast cancer surgery. Recurrent erysipelas accounted for 75.7% of cases. Most patients (89.1%) had at least one comorbidity, with hypertension, diabetes type 2 (DM2), and obesity being the most common. Higher white blood cell (WBC) count, obesity, atrial fibrillation (AF), and the need for enoxaparin administration were independently associated with prolonged hospitalization. Dyslipidemia was significantly associated with erysipelas recurrence (p < 0.05). Conclusions: Both primary and recurrent erysipelas are associated with specific risk factors. Recurrent erysipelas may be linked to components of metabolic syndrome, particularly obesity and dyslipidemia, which emerged as a significant risk factor in this study. Hospitalization length may be prolonged by inflammation markers (WBC and CRP) and comorbidities such as AF, obesity, or the need for enoxaparin in patients with elevated thrombosis risk. Further multicenter studies with larger cohorts are needed to assess the impact of demographics, biomarkers, metabolic disorders, and treatment strategies on erysipelas recurrence and outcomes. Awareness of these risk factors is essential for effective prevention, management, and recurrence reduction. Full article
(This article belongs to the Special Issue Clinical Epidemiology of Skin Diseases: 3rd Edition)
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14 pages, 16834 KiB  
Article
Topical MTH1 Inhibition Suppresses SKP2-WNT5a-Driven Psoriatic Hyperproliferation
by Cecilia Bivik Eding, Ines Köhler, Lavanya Moparthi, Florence Sjögren, Blanka Andersson, Debojyoti Das, Deepti Verma, Martin Scobie, Ulrika Warpman Berglund and Charlotta Enerbäck
Int. J. Mol. Sci. 2025, 26(15), 7174; https://doi.org/10.3390/ijms26157174 - 25 Jul 2025
Viewed by 178
Abstract
Topically applied TH1579 alleviated the psoriatic phenotype in the imiquimod-induced psoriasis mouse model by decreasing CD45+, Ly6b+, and CD3+ cell infiltration and downregulating the expression of the proliferation marker PCNA. Moreover, TH1579 strongly suppressed IL-17 expression in mouse [...] Read more.
Topically applied TH1579 alleviated the psoriatic phenotype in the imiquimod-induced psoriasis mouse model by decreasing CD45+, Ly6b+, and CD3+ cell infiltration and downregulating the expression of the proliferation marker PCNA. Moreover, TH1579 strongly suppressed IL-17 expression in mouse skin, accompanied by reduced infiltration of IL-17-producing γδ-T cells. Furthermore, TH1579 decreased keratinocyte viability and proliferation. Mass spectrometry data analysis revealed the enrichment of proteins associated with nucleotide excision repair and cell cycle regulation. The key cell cycle regulatory protein F-box protein S-phase kinase-associated protein 2 (SKP2) was significantly downregulated, along with the psoriasis-associated proliferation marker WNT5a, identified as a SKP2 downstream target. The downregulation of SKP2 and WNT5a was confirmed in MTH1i-treated mouse skin. Our findings support the topical administration of MTH1i TH1579 as a psoriasis treatment. The therapeutic effects depended on the SKP2/WNT5a pathway, which mediates psoriatic hyperproliferation. This study introduces a conceptually innovative topical treatment for psoriasis patients with mild-to-moderate disease who have limited therapeutic options. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: "Enzyme Inhibition")
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21 pages, 3048 KiB  
Article
Transfersome-Based Delivery of Optimized Black Tea Extract for the Prevention of UVB-Induced Skin Damage
by Nadia Benedetto, Maria Ponticelli, Ludovica Lela, Emanuele Rosa, Flavia Carriero, Immacolata Faraone, Carla Caddeo, Luigi Milella and Antonio Vassallo
Pharmaceutics 2025, 17(8), 952; https://doi.org/10.3390/pharmaceutics17080952 - 23 Jul 2025
Viewed by 313
Abstract
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize [...] Read more.
Background/Objectives: Ultraviolet B (UVB) radiation contributes significantly to skin aging and skin disorders by promoting oxidative stress, inflammation, and collagen degradation. Natural antioxidants such as theaflavins and thearubigins from Camellia sinensis L. (black tea) have shown photoprotective effects. This study aimed to optimize the extraction of theaflavins and thearubigins from black tea leaves and evaluate the efficacy of the extract against UVB-induced damage using a transfersome-based topical formulation. Methods: Extraction of theaflavins and thearubigins was optimized via response surface methodology (Box-Behnken Design), yielding an extract rich in active polyphenols. This extract was incorporated into transfersomes that were characterized for size, polydispersity, zeta potential, storage stability, and entrapment efficiency. Human dermal fibroblasts (NHDF) were used to assess cytotoxicity, protection against UVB-induced viability loss, collagen degradation, and expression of inflammatory (IL6, COX2, iNOS) and matrix-degrading (MMP1) markers. Cellular uptake of the extract’s bioactive marker compounds was measured via LC-MS/MS. Results: The transfersomes (~60 nm) showed a good stability and a high entrapment efficiency (>85%). The transfersomes significantly protected NHDF cells from UVB-induced cytotoxicity, restored collagen production, and reduced gene expression of MMP1, IL6, COX2, and iNOS. Cellular uptake of key extract’s polyphenols was markedly enhanced by the nanoformulation compared to the free extract. Conclusions: Black tea extract transfersomes effectively prevented UVB-induced oxidative and inflammatory damage in skin fibroblasts. This delivery system enhanced bioavailability of the extract and cellular protection, supporting the use of the optimized extract in cosmeceutical formulations targeting photoaging and UV-induced skin disorders. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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13 pages, 1228 KiB  
Brief Report
Lipopolysaccharide-Activated Macrophages Suppress Cellular Senescence and Promote Rejuvenation in Human Dermal Fibroblasts
by Hiroyuki Inagawa, Chie Kohchi, Miyuki Uehiro and Gen-Ichiro Soma
Int. J. Mol. Sci. 2025, 26(15), 7061; https://doi.org/10.3390/ijms26157061 - 22 Jul 2025
Viewed by 297
Abstract
Tissue-resident macrophages are essential for skin homeostasis. This study investigated whether lipopolysaccharide (LPS)-activated macrophages affect senescence and rejuvenation in human dermal fibroblasts. Human monocytic THP-1 cells were stimulated with Pantoea agglomerans–derived LPS (1–1000 ng/mL), and culture supernatants were collected. These were applied [...] Read more.
Tissue-resident macrophages are essential for skin homeostasis. This study investigated whether lipopolysaccharide (LPS)-activated macrophages affect senescence and rejuvenation in human dermal fibroblasts. Human monocytic THP-1 cells were stimulated with Pantoea agglomerans–derived LPS (1–1000 ng/mL), and culture supernatants were collected. These were applied to two NB1RGB fibroblast populations: young, actively dividing cells (Young cells) and senescent cells with high population doubling levels and reduced proliferation (Old cells). Senescence markers P16, P21, and Ki-67 were analyzed at gene and protein levels. Conditioned medium from Old cells induced senescence in Young cells, increasing P16 and P21 expression levels. This effect was suppressed by cotreatment with LPS-activated THP-1 supernatant. Old cells treated with the LPS-activated supernatant exhibited decreased P16 and P21 levels as well as increased Ki-67 expression, indicating partial rejuvenation. These effects were not observed following treatment with unstimulated THP-1 supernatants or LPS alone. Overall, these findings suggest that secretory factors from LPS-activated macrophages can suppress cellular senescence and promote human dermal fibroblast rejuvenation, highlighting the potential role of macrophage activation in regulating cellular aging and offering a promising strategy for skin aging intervention. Full article
(This article belongs to the Special Issue Lipopolysaccharide in the Health and Disease)
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14 pages, 508 KiB  
Review
Could Skin Autofluorescence Be a Useful Biomarker in Systemic Lupus Erythematosus? A Systematic Review
by Teodor Salmen, Claudia Cobilinschi, Andrei Mihăilescu, Bianca-Margareta Salmen, Gabriela-Claudia Potcovaru, Daniela Opris-Belinski, Narcis Copcă, Simona Caraiola, Florentina Negoi, Anca Pantea Stoian and Ioana Săulescu
Int. J. Mol. Sci. 2025, 26(14), 6934; https://doi.org/10.3390/ijms26146934 - 19 Jul 2025
Viewed by 323
Abstract
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease with a heterogeneous organ involvement, for which reliable biomarkers are still being studied. The implication of advanced glycation end products (AGEs), resulting from oxidative stress, and their interaction with the receptor for AGEs (RAGE) [...] Read more.
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease with a heterogeneous organ involvement, for which reliable biomarkers are still being studied. The implication of advanced glycation end products (AGEs), resulting from oxidative stress, and their interaction with the receptor for AGEs (RAGE) has been studied in pathologies with chronic proinflammatory status, offering potential relevance in SLE. This systematic review aimed to evaluate the utility of skin autofluorescence (SAF)—a non-invasive proxy for AGE accumulation—as a biomarker for disease severity, activity, and impact in SLE patients. Following PRISMA guidelines, six studies assessing SAF and/or circulating AGEs and soluble RAGE (sRAGE) in SLE were analyzed. Findings consistently showed higher AGE levels in SLE patients compared to healthy controls, with several correlations between SAF/AGEs and disease features such as SLEDAI scores, organ involvement, inflammatory markers, and damage indices. Decreased sRAGE levels were also observed, possibly due to consumption by AGEs. Some studies further reported predictive associations between specific AGEs or their ratios with sRAGE and particular clinical phenotypes. Although heterogeneity among studies limits definitive conclusions, the AGEs–sRAGE axis—and especially SAF—emerges as a promising candidate for future biomarker development in SLE. Further large-scale longitudinal studies are needed to confirm its clinical utility. Full article
(This article belongs to the Special Issue Molecular Aspects of Autoimmune Diseases)
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16 pages, 2201 KiB  
Article
Oral Squamous Cell Carcinoma Exosomes Upregulate PIK3/AKT, PTEN, and NOTCH Signaling Pathways in Normal Fibroblasts
by Dijana Mitic, Milica Jaksic Karisik, Milos Lazarevic, Jelena Carkic, Emilia Zivkovic, Olivera Mitrovic Ajtic and Jelena Milasin
Curr. Issues Mol. Biol. 2025, 47(7), 568; https://doi.org/10.3390/cimb47070568 - 19 Jul 2025
Viewed by 351
Abstract
Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. [...] Read more.
Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. Magnetic sorting was applied to obtain pure exosomes. Morphology and size were characterized by transmission electron microscopy and nanoparticle tracking analysis. Validation of membrane exosomal markers (CD9, CD63) was performed via Western blotting. MiR-21, miR-31, and miR-133 levels were analyzed in exosomes and parent cells by qPCR. Biological effects of the exosomes were tested by adding them to fibroblast cultures and determining the expression of relevant carcinogenesis markers by qPCR. Exosomes appeared as cup-shaped nano-sized particles, and there was no difference regarding particle diameter and concentration between the three types of exosomes. The oncogenic miR-21 was significantly upregulated both in SCC and SCC-derived exosomes compared to DOK and HaCaT cells and their respective exosomes. However, miR-31 unexpectedly showed the highest expression in normal cells and the lowest in HaCaT exosomes. MiR-133, the tumor suppressor miRNA, was downregulated in both SCC and DOK cells compared to normal (HaCaT) cells, while the opposite situation was observed in exosomes, with HaCaT cells showing the lowest levels of miR-133. The differences in exosome content were reflected in signaling pathway activation in exosome-treated fibroblasts, with SCC exosomes exerting the most potent effect on several cancer-related pathways, notably PIK3/AKT, PTEN, and NOTCH signaling cascades. Full article
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26 pages, 6375 KiB  
Article
Photoprotective Effects of Quercetin and Hesperidin in Polymorphous Light Eruption: A Comparative Study with Alpha-Glucosylrutin
by Yoon-Seo Choi, Sang-Hoon Park, Inhee Jung, Eun-Ju Park, Wonki Hong, Jin-Hee Shin, Won-Sang Seo and Jongsung Lee
Curr. Issues Mol. Biol. 2025, 47(7), 567; https://doi.org/10.3390/cimb47070567 - 19 Jul 2025
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Abstract
Polymorphous Light Eruption (PLE) is a prevalent UV-induced photodermatosis characterized by abnormal immune responses, oxidative stress, and cutaneous inflammation. Alpha-glucosylrutin (AGR), a chemically modified flavonoid widely used for its antioxidant and photoprotective effects, has shown clinical efficacy; however, its synthetic origin and classification [...] Read more.
Polymorphous Light Eruption (PLE) is a prevalent UV-induced photodermatosis characterized by abnormal immune responses, oxidative stress, and cutaneous inflammation. Alpha-glucosylrutin (AGR), a chemically modified flavonoid widely used for its antioxidant and photoprotective effects, has shown clinical efficacy; however, its synthetic origin and classification as a potential skin sensitizer and aquatic toxin raise safety and environmental concerns. These limitations underscore the need for safer, naturally derived alternatives. In this study, we investigated the comparative efficacy of quercetin (QC) and hesperidin (HPN)—two plant-based flavonoids—against AGR in in vitro and ex vivo models of sun-induced skin damage. An optimized QC:HPN 8:1 (w/w) complex significantly restored antioxidant enzyme activities (SOD: 4.11 ± 0.32 mU/mg; CAT: 1.88 ± 0.04 mU/mg) and suppressed inflammatory cytokine production (IL-6: 155.95 ± 3.17 pg/mL; TNF-α: 62.34 ± 0.72 pg/mL) more effectively than AGR. β-hexosaminidase secretion, a marker of allergic response, was reduced to 99.02 ± 1.45% with QC:HPN 8:1, compared to 121.33 ± 1.15% with AGR. QC alone exhibited dose-dependent cytotoxicity at ≥10 μg/mL, whereas HPN maintained >94% cell viability at all tested concentrations. These findings highlight the QC:HPN 8:1 complex as a safe, natural, and effective alternative to synthetic AGR for preventing and managing PLE and UV-induced dermal inflammation. Further research should focus on clinical validation and formulation development for topical use. Full article
(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products, 3rd Edition)
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