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Search Results (1,210)

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Keywords = skin immune responses

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2 pages, 137 KiB  
Abstract
A Clinically Relevant Cationic Adjuvant System Induces Th17 T Cells Involved in Skin and Upper Airway Infections with Streptococcus pyogenes
by Kristoffer Mazanti Melchiors, Nina Dieu Nhien Tran Nguyen, Sharmila Subratheepam, Ida Rosenkrands, Frank Follmann and Jes Dietrich
Proceedings 2025, 124(1), 3; https://doi.org/10.3390/proceedings2025124003 - 6 Aug 2025
Abstract
Streptococcus pyogenes (Group A Streptococcus, StrepA) is a human pathogen responsible for hundreds of millions of infections each year and remains one of the most prevalent bacterial causes of upper respiratory and skin infections worldwide. Despite its global impact, there is no [...] Read more.
Streptococcus pyogenes (Group A Streptococcus, StrepA) is a human pathogen responsible for hundreds of millions of infections each year and remains one of the most prevalent bacterial causes of upper respiratory and skin infections worldwide. Despite its global impact, there is no approved vaccine, and the optimal protective immune response is still not fully understood. In particular, the role of Th17 T cells in immunity against StrepA remains to be explored. We have previously shown that Th17 T cells are induced in humans following StrepA infection. In this study, we investigated the role of Th17 T cells during skin and upper airway StrepA infections. To generate StrepA-specific Th17 T cells, we utilized a novel cationic liposomal adjuvant system. We demonstrated that vaccine-induced Th17 T cells are recruited to the skin and upper airways upon StrepA infection. In the airways, Th17 T cells and IgA correlate with protection, whereas Th1 T cells and IgG do not. To further characterize the recruited Th17 T cells, we used an IL-17 fate-reporter mouse model to track Th17 T cells. Our results show that Th17 T cells outnumber bona fide Th1 T cells in both StrepA-infected skin and upper airways. Surprisingly, most Th17 T cells lose expression of IL-17, and do not express TNFα, IFNγ, and IL-2. Initial single-cell sequencing data suggest the existence of multiple Th17 T cell subsets with distinct expression profiles. We discuss the functional relevance of these subsets in the context of a StrepA infection. Full article
23 pages, 1610 KiB  
Article
Unraveling the Systemic and Local Immune Response of Rainbow Trout (Oncorhynchus mykiss) to the Viral Hemorrhagic Septicemic Virus
by Mariana Vaz, Gonçalo Espregueira Themudo, Felipe Bolgenhagen Schöninger, Inês Carvalho, Carolina Tafalla, Patricia Díaz-Rosales, Lourenço Ramos-Pinto, Benjamín Costas and Marina Machado
Biology 2025, 14(8), 1003; https://doi.org/10.3390/biology14081003 - 5 Aug 2025
Abstract
Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout [...] Read more.
Viral outbreaks have caused significant mortality and economic losses in aquaculture, highlighting the urgent need for effective therapies and a deeper understanding of antiviral and immune mechanisms in key species. This study investigates the constitutive and virus-induced antiviral responses in juvenile rainbow trout (Oncorhynchus mykiss) following infection with viral hemorrhagic septicemia virus (VHSV). Trout (30 g) were infected by immersion with VHSV (TCID50 = 105 mL−1) for two hours. Samples were collected at 24, 72, and 120 h post-infection to assess hematology, innate immunity, viral load, and transcriptomic response. At 24 h post-infection, no immune response or increase in viral load was detected, suggesting the host had not yet recognized the virus and was still in the incubation phase. By 72 h, viral replication peaked, with high viral loads observed in mucosal tissues (skin and gills) and immune organs (kidney, spleen, liver), alongside strong up-regulation of antiviral genes, such as viperin. This gene maintained high expression through the final sampling point, indicating its key role in the antiviral response. At this stage, reduced immune competence was observed, marked by elevated nitric oxide and circulating thrombocytes. At 120 h, modest increases in peripheral monocyte, plasma lysozyme, and peroxidase activity were detected; however, these responses were insufficient to reduce viral load, suggesting the resolution phase had not yet begun. In summary, while a limited immune response was observed by the end of the trial, the consistent antiviral activity of viperin from peak infection to 120 h post-infection underscores its importance in the defence against VHSV in rainbow trout. Full article
(This article belongs to the Section Immunology)
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24 pages, 2475 KiB  
Article
An Immunomodulating Peptide with Potential to Promote Anticancer Immunity Without Compromising Immune Tolerance
by Michael Agrez, Christopher Chandler, Amanda L. Johnson, Marlena Sorensen, Kirstin Cho, Stephen Parker, Benjamin Blyth, Darryl Turner, Justyna Rzepecka, Gavin Knox, Anastasia Nika, Andrew M. Hall, Hayley Gooding and Laura Gallagher
Biomedicines 2025, 13(8), 1908; https://doi.org/10.3390/biomedicines13081908 - 5 Aug 2025
Abstract
Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the [...] Read more.
Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article
(This article belongs to the Special Issue Peptides and Amino Acids in Drug Development: Here and Now)
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29 pages, 21916 KiB  
Article
Pentoxifylline and Norcantharidin Synergistically Suppress Melanoma Growth in Mice: A Multi-Modal In Vivo and In Silico Study
by Israel Lara-Vega, Minerva Nájera-Martínez and Armando Vega-López
Int. J. Mol. Sci. 2025, 26(15), 7522; https://doi.org/10.3390/ijms26157522 - 4 Aug 2025
Abstract
Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly [...] Read more.
Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article
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17 pages, 5703 KiB  
Review
IFN γ and the IFN γ Signaling Pathways in Merkel Cell Carcinoma
by Lina Song, Jinye Guan, Qunmei Zhou, Wenshang Liu, Jürgen C. Becker and Dan Deng
Cancers 2025, 17(15), 2547; https://doi.org/10.3390/cancers17152547 - 1 Aug 2025
Viewed by 181
Abstract
Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, [...] Read more.
Recent preclinical and clinical studies have confirmed the essential role of interferons in the host’s immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30–56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ’s crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ–based interventions in MCC. Full article
(This article belongs to the Special Issue Histopathology and Pathogenesis of Skin Cancer)
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17 pages, 2388 KiB  
Review
Interactions Between Prolactin, Intracellular Signaling, and Possible Implications in the Contractility and Pathophysiology of Asthma
by Eduardo Calixto, Juan C. Gomez-Verjan, Marco Cerbón, Valeria Rodríguez-Chávez, Bianca S. Romero-Martínez, María E. Martinez-Enriquez, Luis M. Montaño, Héctor Solís-Chagoyán, Arnoldo Aquino-Gálvez, Nadia A. Rivero-Segura, Georgina González-Ávila, Ana del Carmen Susunaga Notario, Gloria E. Pérez-Figueroa, Verónica Carbajal, Edgar Flores-Soto and Bettina Sommer
Int. J. Mol. Sci. 2025, 26(15), 7332; https://doi.org/10.3390/ijms26157332 - 29 Jul 2025
Viewed by 356
Abstract
Prolactin (PRL) is a hormone primarily associated with lactation, but it plays various roles in both men and women. PRL belongs to the family of peptide hormones, including placental lactogen and growth hormone. Interestingly, PRL is a pleiotropic hormone affecting several physiological and [...] Read more.
Prolactin (PRL) is a hormone primarily associated with lactation, but it plays various roles in both men and women. PRL belongs to the family of peptide hormones, including placental lactogen and growth hormone. Interestingly, PRL is a pleiotropic hormone affecting several physiological and pathological conditions, including fertility. Moreover, several pathophysiological roles have been associated with this hormone, including those of the immune system, autoimmune disorders, asthma, and ageing. Additionally, PRL receptors are ubiquitously expressed in tissues, including the mammary gland, gonads, liver, kidney, adrenal gland, brain, heart, lungs, pituitary gland, uterus, skeletal muscle, skin blood cells, and immune system. Therefore, in the present paper, we cover the potential role that PRL may play in asthma by promoting inflammation and modulating immune responses. The detection of its receptor in lung tissue suggests a direct role in airway smooth muscle contractility through activation of signaling pathways such as JAK2-STAT5, MAPK/ERK1/2, and PI3K/Akt, as well as influencing ionic currents that regulate cell contraction, proliferation, and survival. In this sense, this review aims to explore the potential involvement of PRL in asthma pathophysiology by examining its interactions with intracellular signaling pathways and its possible impact on airway smooth muscle contractility and immune modulation. Full article
(This article belongs to the Special Issue New Insights into Airway Smooth Muscle: From Function to Dysfunction)
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33 pages, 4819 KiB  
Review
Hydrogels Modulating the Microbiome: Therapies for Tissue Regeneration with Infection Control
by Germán Reynaldo Jiménez-Gastelum, Carlos Esteban Villegas-Mercado, Juan Luis Cota-Quintero, Silvia Ivonne Arzola-Rodríguez, Rosalío Ramos-Payán and Mercedes Bermúdez
Gels 2025, 11(8), 584; https://doi.org/10.3390/gels11080584 - 29 Jul 2025
Viewed by 431
Abstract
This review explores the emerging role of functionalized hydrogels in modulating the microbiome for therapeutic applications in tissue regeneration and infection control. The skin and gut microbiomes play crucial roles in maintaining tissue homeostasis, regulating immune responses, and influencing the healing process. Disruptions [...] Read more.
This review explores the emerging role of functionalized hydrogels in modulating the microbiome for therapeutic applications in tissue regeneration and infection control. The skin and gut microbiomes play crucial roles in maintaining tissue homeostasis, regulating immune responses, and influencing the healing process. Disruptions in microbial balance—such as those observed in chronic wounds, autoimmune conditions, or post-surgical environments—can impair regeneration and increase susceptibility to infection. Hydrogels, due to their tunable physical and chemical properties, serve as versatile platforms for delivering probiotics, prebiotics, antimicrobials, and immune-modulatory agents. The encapsulation of beneficial bacteria, such as Lactobacillus plantarum or Prevotella histicola, within hydrogels could enhance bacterial viability, targeted delivery, and immune tolerance. Additionally, hydrogels functionalized with silver nanoparticles, nitric oxide donors, and bacteriocins have demonstrated effective biofilm disruption and pathogen clearance. These systems also promote favorable immune responses, such as M2 macrophage polarization and the induction of regulatory T cells, which are essential for tissue repair. Innovative approaches, including 3D bioprinting, self-healing materials, and photothermal-responsive hydrogels, expand the clinical versatility of these systems. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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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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26 pages, 1300 KiB  
Review
The Human Mycobiome: Composition, Immune Interactions, and Impact on Disease
by Laura Carrillo-Serradell, Jade Liu-Tindall, Violeta Planells-Romeo, Lucía Aragón-Serrano, Marcos Isamat, Toni Gabaldón, Francisco Lozano and María Velasco-de Andrés
Int. J. Mol. Sci. 2025, 26(15), 7281; https://doi.org/10.3390/ijms26157281 - 28 Jul 2025
Viewed by 692
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular Biology)
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18 pages, 630 KiB  
Review
Unravelling the Link Between Hidradenitis Suppurativa and Inflammatory Bowel Disease: A Literature Review
by Konstantinos Mpakogiannis, Fotios S. Fousekis, Emmanouil Karampinis, Eleftheria Mastoridou, Georgios Gaitanis and Konstantinos H. Katsanos
Biomedicines 2025, 13(8), 1833; https://doi.org/10.3390/biomedicines13081833 - 27 Jul 2025
Viewed by 544
Abstract
Hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated conditions with significant impact on quality of life. Emerging evidence reveals a notable epidemiological and pathogenic overlap between HS and IBD, particularly CD. Although [...] Read more.
Hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated conditions with significant impact on quality of life. Emerging evidence reveals a notable epidemiological and pathogenic overlap between HS and IBD, particularly CD. Although a bidirectional association between HS and IBD has been well documented, current evidence supports a causal effect of IBD on the development of HS, while a causal relationship in the opposite direction has yet to be established. The present review explores the important association between these immune-mediated conditions and further highlights shared risk factors, genetic predispositions and immunopathogenic mechanisms, such as dysbiosis and cytokine dysregulation, involved in both HS and IBD. Diagnostic challenges, especially in differentiating perianal HS from perianal CD, are also discussed. The coexistence of HS and IBD impacts disease severity, treatment response, and overall management strategies. Shared therapeutic approaches, such as TNF-α inhibitors and JAK inhibitors, are considered promising options for effectively managing patients affected by both conditions. Nevertheless, deeper understanding of the gut–skin axis that will offer potential for more precise interventions in patients with simultaneous HS and IBD is considered imperative. Full article
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16 pages, 697 KiB  
Article
Association Study of PDCD1 Gene Variants and Its Gene Expression with Cutaneous Melanoma in a Mexican Population
by Fernando Valdez-Salazar, Luis A. Jiménez-Del Rio, Elizabeth Guevara-Gutiérrez, Andrea Melissa Mendoza-Ochoa, María José Zorrilla-Marina, Diana Karla García-Nuño, Jorge R. Padilla-Gutiérrez, José F. Muñoz-Valle and Emmanuel Valdés-Alvarado
Genes 2025, 16(8), 866; https://doi.org/10.3390/genes16080866 - 24 Jul 2025
Viewed by 254
Abstract
Background/Objectives: Melanoma is an aggressive skin cancer influenced by genetic and immunological factors. The PDCD1 gene encodes PD-1, a receptor involved in immune evasion and therapeutic response. This study aimed to evaluate the association of PDCD1 variants (rs2227982, rs36084323, rs7421861) and its [...] Read more.
Background/Objectives: Melanoma is an aggressive skin cancer influenced by genetic and immunological factors. The PDCD1 gene encodes PD-1, a receptor involved in immune evasion and therapeutic response. This study aimed to evaluate the association of PDCD1 variants (rs2227982, rs36084323, rs7421861) and its relative gene expression with melanoma in a Mexican population. Methods: An analytical cross-sectional study was conducted with 262 samples: 131 from melanoma patients (newly diagnosed and treatment-naïve) and 131 from cancer-free controls. Genotyping was performed using real-time PCR. PDCD1 expression was assessed by qPCR, normalized with GAPDH, using the 2−ΔΔCt method and the Pfaffl model. Statistical comparisons included allele/genotype frequencies, expression levels, and clinicopathological associations. Results: No significant association was found between the studied PDCD1 variants and melanoma susceptibility. However, PDCD1 was significantly overexpressed in melanoma samples (2.42-fold increase; p < 0.01), consistent across both quantification methods. Significant associations were also observed between histopathological subtype and Breslow thickness, and between subtype and anatomical site (p < 0.01). Conclusions: Although PDCD1 variants showed no association with melanoma risk, the gene’s overexpression highlights its potential relevance in melanoma immunobiology. These findings contribute to the molecular characterization of melanoma in the Mexican population and support future research on PDCD1 as an immunological biomarker. Full article
(This article belongs to the Section Population and Evolutionary Genetics and Genomics)
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19 pages, 1046 KiB  
Review
Roles of Peripheral Nerves in Tumor Initiation and Progression
by Claudia Giampietri, Elisa Pizzichini, Francesca Somma, Simonetta Petrungaro, Elena De Santis, Siavash Rahimi, Antonio Facchiano and Cinzia Fabrizi
Int. J. Mol. Sci. 2025, 26(15), 7064; https://doi.org/10.3390/ijms26157064 - 22 Jul 2025
Viewed by 456
Abstract
In recent years, a long list of relevant studies has highlighted the engagement of the nervous system in the fine-tuning of tumor development and progression. Several authors have shown that different types of nerve fibres (sympathetic, parasympathetic/vagal or somatosensory fibres) may contribute to [...] Read more.
In recent years, a long list of relevant studies has highlighted the engagement of the nervous system in the fine-tuning of tumor development and progression. Several authors have shown that different types of nerve fibres (sympathetic, parasympathetic/vagal or somatosensory fibres) may contribute to tumor innervation affecting cancer initiation, progression and metastasis. A large presence of nerve fibres is frequently observed in tumors with respect to the corresponding healthy tissues. In this regard, it is worth noting that in some cases a reduced innervation may associate with slow tumor growth in a tissue-specific manner. Current studies have begun to shed light over the role played in this specific process by Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system. SCs observed in cancer tissues share strong similarities with repair SCs that appear after nerve injury. A large body of research indicates that SCs may have a role in shaping the microenvironment of tumors by regulating the immune response and influencing their invasiveness. In this review, we summarize data relevant to the role of peripheral innervation in general, and of SCs in particular, in defining the progression of different tumors: melanoma that originate in the skin with mainly sensory innervation; pancreatic and liver-derived tumors (e.g., pancreatic adenocarcinoma and cholangiocarcinoma) with mainly autonomous innervation. We conclude by summarizing data regarding hepatocarcinoma (with anatomical predominance of small autonomic nerve fibres) in which the potential relationship between innervation and tumor progression has been little explored, and largely remains to be defined. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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24 pages, 327 KiB  
Review
Genetic Landscape of Kawasaki Disease: An Update
by Taru Goyal, Saniya Sharma, Rakesh Kumar Pilania, Kajol Jawallia, Sanchi Chawla, Madhubala Sharma, Monica Rawat, Vaishali Thakur, Urvi Arya, Anoop Kumar, Manpreet Dhaliwal, Vignesh Pandiarajan, Amit Rawat and Surjit Singh
Lymphatics 2025, 3(3), 21; https://doi.org/10.3390/lymphatics3030021 - 20 Jul 2025
Viewed by 318
Abstract
Kawasaki disease (KD), first identified in 1967 by Dr. Tomisaku Kawasaki, is an acute, self-limited vasculitis and remains the leading cause of acquired heart disease in children worldwide, particularly affecting those under the age of five. Clinically, it presents with persistent fever, mucocutaneous [...] Read more.
Kawasaki disease (KD), first identified in 1967 by Dr. Tomisaku Kawasaki, is an acute, self-limited vasculitis and remains the leading cause of acquired heart disease in children worldwide, particularly affecting those under the age of five. Clinically, it presents with persistent fever, mucocutaneous inflammation, skin rashes, and lymphadenopathy, with a marked tendency to involve the coronary arteries, potentially leading to serious complications such as coronary artery aneurysms. Despite extensive research spanning more than five decades, the precise etiology of KD remains unclear. However, accumulating evidence supports the significant role of genetic predisposition, highlighting the contribution of inherited factors in modulating immune responses and influencing disease susceptibility and severity. Emerging evidence highlights genetic susceptibility as pivotal, with genome-wide studies identifying polymorphisms in immune-related genes, such as ITPKC, CASP3, BLK, CD40, and ORAI1, which modulate disease risk and coronary complications. Epigenetic mechanisms, including DNA methylation and non-coding RNAs, bridge the gap between genetic and environmental factors, regulating immune responses and endothelial activation. Furthermore, emerging insights into autophagy-related processes provide a deeper understanding of the molecular mechanisms underlying the disease. This review aims to explore the current knowledge on the genetic landscape of KD, examine how these findings contribute to our understanding of its pathophysiology, and investigate the potential for genetically targeted therapeutic strategies in the future. Full article
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
Viewed by 511
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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18 pages, 5007 KiB  
Article
Integrated Multi-Omics Profiling Reveals That Highly Pyroptotic MDMs Contribute to Psoriasis Progression Through CXCL16
by Liping Jin, Xiaowen Xie, Mi Zhang, Wu Zhu, Guanxiong Zhang and Wangqing Chen
Biomedicines 2025, 13(7), 1763; https://doi.org/10.3390/biomedicines13071763 - 18 Jul 2025
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Abstract
Background: Psoriasis, an inflammatory skin disorder, involves pyroptosis—a pro-inflammatory cell death process. However, cell-specific pyroptosis dynamics and immune microenvironment interactions remain unclear. Objective: To investigate cell-type-specific pyroptosis patterns in psoriasis and their immunoregulatory mechanisms. Methods: We integrated 21 transcriptomic datasets (from 2007 to [...] Read more.
Background: Psoriasis, an inflammatory skin disorder, involves pyroptosis—a pro-inflammatory cell death process. However, cell-specific pyroptosis dynamics and immune microenvironment interactions remain unclear. Objective: To investigate cell-type-specific pyroptosis patterns in psoriasis and their immunoregulatory mechanisms. Methods: We integrated 21 transcriptomic datasets (from 2007 to 2020) obtained from the GEO database and two single-cell RNA sequencing datasets to quantify pyroptotic activity using Gene Set Variation Analysis and AUCell algorithms. Immune cell infiltration profiles were evaluated via CIBERSORT, while cell-cell communication networks were analyzed by CellChat. In vitro and in vivo experiments were performed to validate key findings. Results: Our analysis revealed that psoriasis patients exhibited significantly elevated levels of pyroptosis compared to healthy controls, with pyroptotic activity reflecting treatment responses. Notably, monocyte-derived macrophages (MDMs) in psoriatic lesions displayed markedly heightened pyroptotic activity. In vitro experiments confirmed that MDMs derived from psoriasis patients overexpressed pyroptosis-related molecules (Caspase 1 and Caspase 4) as well as pro-inflammatory cytokines (TNFα, IL6, IL1β) when compared to healthy controls. Furthermore, these cells showed increased expression of CXCL16, which might potentially activate Th17 cells through CXCR6 signaling, thereby driving skin inflammation. Inhibition of monocyte migration in an imiquimod-induced psoriasiform dermatitis model significantly alleviated skin inflammation and reduced the proportion of M1 macrophages and Th17 cells in lesional skin. Conclusions: This study revealed that MDMs in psoriatic lesions exhibited a hyperactive pyroptotic state, which contributed to disease progression through CXCL16-mediated remodeling of the immune microenvironment. These findings highlight pyroptosis as a potential therapeutic target for psoriasis. Full article
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