Search Results (7,200)

Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8⁺ T cells playing a central pathogenic role, yet the mechanisms driving their hyperactivation remain unclear. Lactate has emerged as a key immunometabolite that functions as both a signaling molecule and an epigenetic modulator via protein lactylation. Nevertheless, the role of lactate in vitiligo pathogenesis has not been explored. Here, we report that serum lactate levels are significantly elevated in vitiligo patients and correlate positively with disease activity. In a mouse model, lactate administration accelerated vitiligo progression, accompanied by increased CD8⁺ T cell infiltration and melanocyte destruction in lesional skin. In vitro, lactate enhanced CD8⁺ T cell effector molecule expression (granzyme B, perforin, IFN-γ, CD107a) and cytotoxic function. Mechanistically, lactate increased global protein lactylation in CD8⁺ T cells, with marked enrichment at histone H3 lysine 9 (H3K9). H3K9 lactylation (H3K9la) was associated with enhanced chromatin accessibility and transcriptional activation of effector genes, as revealed by RNA sequencing and CUT&Tag analyses. Pharmacological inhibition of lactate production or lactylation abrogated these effects. Collectively, our findings identify lactate as a critical driver of CD8⁺ T cell pathogenicity in vitiligo through H3K9la-mediated epigenetic reprogramming, highlighting lactate metabolism and lactylation as potential therapeutic targets. Full article

NLRP1 is an inflammasome sensor protein expressed in barrier tissues of humans. Its activation in response to microbes or cellular stress triggers a cascade of molecular events, leading up to IL1β-driven inflammation and pyroptosis. Rare germline mutations of NLRP1 cause its persistent activation, resulting in autoinflammatory syndromes. Multiple self-healing palmoplantar carcinoma (MSPC) is one such syndrome, characterized by the appearance of recurrent keratoacanthomas (KAs) on the palms and soles. Here, we aimed to compare the subcellular localization of mutant NLRP1 in lesions from an MSPC patient to wild-type NLRP1 in non-MSPC-KAs and in skin from healthy donors. Using mass spectrometry, immunohistochemistry and immunoelectron tomography, we found that NLRP1 localized to mast cell granules in all MSPC lesions but also in healthy skin, a novel finding which implicates these cells in NLRP1-associated responses in human skin. Moreover, we found that mast cells expressing the A66V pathogenic variant of NLRP1 overpopulated MSPC-KAs, infiltrated the epidermis and degranulated, a behavior not seen in other lesions from this study. The released granules had the highest NLRP1 protein content and also contained NLRP3 and IL1β, suggesting the coexistence of inflammasome pathways within mast cells. Taken together, our findings propose cutaneous mast cells as a previously unrecognized NLRP1 reservoir in health and disease. Full article

Melanoma is a heterogeneous, complex and aggressive disease that, despite recent advances in molecular-targeted drugs and molecular and genetic analysis, represents approximately 65% of skin cancer deaths, and unfortunately survival dramatically decreases in melanoma stages III/IV. In young people there is an increased incidence of developing melanoma; hence new therapeutic strategies must be urgently investigated. Peptidergic systems play a crucial role in these strategies to fight melanoma. The scope of this review is to show the enormous potential of targeting peptidergic systems alone or in combination therapy with standard therapeutic strategies currently used in clinical practice to treat melanoma. In this sense, key points such as peptidergic systems and anti-melanoma treatments, oncogenic/anti-melanoma peptides, peptide receptors, peptidergic systems, melanoma risk and immune system relationships, clinical relevance, peptidergic systems and delivery strategies in melanoma will be discussed. Peptides exert oncogenic, anti-melanoma and dual oncogenic and anti-melanoma effects in melanoma, showing a high functional complexity in regulating melanoma development. A plethora of anti-melanoma strategies have been developed or repurposed for potential clinical applications, including peptide/peptide receptor antibodies, peptide receptor antagonists or agonists, enzyme inhibitors, CAR-macrophages, microRNAs and vaccines. Strategies for peptide delivery and protection from enzymatic degradation have also been developed. Some of the previous anti-melanoma strategies are based on the expression/overexpression of peptide receptors in melanoma cells which is crucial for diagnosis, melanoma risk and progression and metastasis development and for the application of more specific and safer anti-melanoma strategies. A meticulous and in-depth study of the peptidergic systems may help to understand how peptidergic systems regulate melanoma progression and shed light on possible therapeutic applications that can be applied in clinical practice. This review shows the enormous potential of targeting peptidergic systems alone or in combination therapy with standard therapeutic strategies currently used in clinical practice to treat melanoma. The benefits to be gained from these studies will be enormous because the peptidergic systems are promising antitumor targets in melanoma, based on the numerous anti-melanoma strategies that have been developed until now. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease linked to epidermal barrier dysfunction, Th2-skewed immune polarization, and disrupted gut microbiota homeostasis. While probiotic interventions show promise in managing AD, the mechanisms governing strain-specific efficacy—particularly systemic modulation via the “gut–skin axis”—remaining to be fully elucidated. Methods: This study systematically compared the oral therapeutic effects of three Lacticaseibacillus rhamnosus strains (MG-A047, MG-A054, and LGG) in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Results: By integrating behavioral, histopathological, and serological assessments with 16S rRNA-based gut microbiota profiling and in vitro functional assays, this study offers a multidimensional evaluation of the strain-specific advantages and potential therapeutic mechanisms of three L. rhamnosus strains. The results demonstrate that MG-A054 most effectively alleviated cutaneous inflammation and pruritus, significantly reduced serum IgE and IL-4 levels, and attenuated epidermal hyperplasia and inflammatory cell infiltration (including mast cells and eosinophils). Mechanistically, this strain may directly inhibit hyaluronidase activity and mast cell degranulation, and specifically remodel the gut microbiota structure, thereby promoting a shift toward a healthier functional profile. Conclusions: These findings suggest that the superior efficacy of MG-A054 may be achieved through coordinated modulation of the gut–skin axis and related pathways. This study offers new mechanistic clues for understanding the strain-specific actions of probiotics and lays a preclinical foundation for the further development of MG-A054 as a potential targeted microecological therapy for AD. Full article

Chronic skin inflammatory diseases including psoriasis and atopic dermatitis affect millions worldwide, imposing substantial physical, psychological, and economic burdens. Despite advances in topical therapies, conventional formulations suffer from poor skin penetration, rapid clearance, local and systemic side effects, and suboptimal patient adherence. Polymeric nanogels, internally crosslinked three-dimensional polymer networks with dimensions of 10–200 nm, emerged as promising platforms to overcome these limitations. Their unique properties including high water content, tunable porosity, biocompatibility, deformability, and stimulus-responsive behavior enhance skin penetration allowing for targeted therapeutic action. This review examines nanogel synthesis methods optimized for targeting skin inflammatory diseases, including biopolymer-based approaches utilizing chitosan and hyaluronic acid, offering insights into how different methods and advanced architecture provide multifunctional capacities and bioactivities. Translation challenges including manufacturing scalability, long-term safety assessment, and regulatory compliance are critically discussed alongside emerging opportunities in personalized medicine and smart microneedle integrated systems for adaptive therapy. Full article

The utilization of immunomodulatory nanomaterials, i.e., leveraging their unique properties to enhance immune responses, represents a transformative approach for the treatment of various diseases. Recent advancements in nanotechnology have enabled the design of nanomaterials capable of delivering immunomodulatory agents in a targeted manner, such as cytokines, antibodies, and nucleic acids, to specific cells or tissues involved in immune regulation. These nanomaterials, including nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, MXenes and extracellular vesicles, have been increasingly tailored to modulate immune responses with precision and efficacy. This targeted approach not only enhances therapeutic outcomes but also reduces off-target effects, minimizing systemic toxicity. In this review, an overview of immunomodulatory nanomaterials and their biomedical applications are highlighted. Herein, we have discussed different types of nanomaterials and their design strategies, interactions with different immune system components (macrophages, dendritic cells (DCs), neutrophils, T lymphocytes (CD4⁺ helper T-cells, CD8⁺ cytotoxic T-cells, regulatory T-cells/Tregs, and memory T-cells), and B lymphocytes), and immunomodulation mechanisms. Furthermore, nanomaterial-based immunomodulation strategies to enhance cancer immunotherapy, wound healing, and bone regeneration and the treatment of infectious diseases, autoimmune diseases, and allergy and are discussed in detail. In addition to therapeutic applications, selected nanomaterial platforms demonstrate significant potential in pharmaceutical formulations by improving drug stability, controlled release, and bioavailability, as well as in cosmetology through skin-targeted delivery, anti-inflammatory activity, immune protection, and enhanced tissue regeneration. Finally, clinical trial updates, challenges and future prospects are outlined. Key findings indicate that lipid-based, polymeric, inorganic nanoparticles and dendrimers provide complementary advantages for immunomodulation, including efficient delivery, controlled release, multifunctionality, and precise immune targeting. Despite safety, regulatory, and scalability challenges, these systems show strong potential for advancing precision and personalized medicine. Taken together, these innovations hold great promise for personalized medicine approaches, wherein nanomaterials can be tailored to individual patient profiles for more effective and precise disease treatment and prevention strategies. This review focuses primarily on the mechanistic interactions between immunomodulatory nanomaterials and immune cells, including macrophages, dendritic cells, neutrophils, T lymphocytes, and B lymphocytes, rather than providing an exhaustive treatment of physicochemical optimization parameters such as particle size or surface modification chemistry, which fall outside the defined scope of this work. Full article

This study investigates shared molecular mechanisms between pyoderma gangrenosum (PG) and inflammatory bowel disease (IBD) and systematically evaluates the therapeutic potential of JAK inhibitors targeting this pathway. Despite the clear clinical comorbidity, the core inflammatory pathways driving cross-tissue associations between the two diseases remain unclear. Furthermore, systematic mechanistic evidence is lacking regarding whether JAK inhibitors act by regulating shared pathological pathways in patients with comorbidities. To address this, this study integrated PG skin and IBD intestinal transcriptome data, single-cell transcriptomic data, and genome-wide association study (GWAS) meta-data from public databases. It employed a multi-level computational biology approach combining Mendelian randomization, weighted gene co-expression network analysis, protein interaction network construction, molecular docking simulations, and system dynamics modeling. The results revealed that genetic analysis confirmed IBD as a causal risk factor for PG, precisely identifying six shared genetic loci. Transcriptomic analysis identified a cross-tissue conserved inflammatory module centered on the JAK-STAT pathway, with JAK2 and STAT3 identified as network hubs. Molecular docking predicted high affinity of baricitinib for both JAK1 and JAK2, while system dynamics modeling demonstrated that its intervention effectively suppresses signaling in the shared inflammatory network. This study reveals the molecular basis of the “gut–skin axis” comorbidity between PG and IBD from a multi-omics integration perspective. It provides predictive computational evidence for the use of JAK inhibitors in targeted comorbidity therapy. Baricitinib is identified as a particularly promising candidate. These findings advance the transition from empirical drug use to mechanism-guided precision treatment strategies. Although this study provides multiscale computational simulation evidence, the lack of direct experimental validation of these predicted results necessitates further confirmation through in vitro and in vivo experiments. Full article

Background: Lumpy skin disease (LSD) is caused by a Capripoxvirus. Live attenuated vaccines, which are commercially available, could be not safe because of the side effects. The aim of this study was the evaluation of the safety, immunogenicity, and effects on the qualitative and quantitative parameters of milk. The feasibility of identifying vaccinated animals using our inactivated vaccine in dairy cows was analysed. The vaccine was tested in guinea pigs as an immunogenicity predictive model. Methods: LSD virus was propagated on Madin–Darby Bovine Kidney (MDBK) cells, then inactivated and supplemented with keyhole limpet hemocyanin (KLH) protein, obtaining a positive marker vaccine. This was inoculated in guinea pigs and in dairy cows, and animal sera were analysed using enzyme-linked immunosorbent assay (ELISA) and a serum neutralisation (SN) test. Quantitative and qualitative analyses were performed on milk. Results: The vaccine was previously tested for efficacy in vaccinated calves, showing a pronounced reduction in clinical symptoms after challenge. The safety and immunogenicity obtained in calves were also confirmed in dairy cows in this study. In fact, high values of the SN test (1:20 to 1:80) and ELISA (90 and 240 S/P%) were obtained after vaccination. Moreover, high immunogenicity of the vaccine was also assessed in guinea pigs. In addition, the results of the milk analyses did not show any differences between vaccinated and control groups. The KLH was able to elicit an immune response detectable using an ELISA (3.0 and 3.5 optical density values). Finally, our vaccine could be used to reduce LSD symptoms and identify vaccinated animals. Full article

Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting both the joints and skin. Beyond musculoskeletal manifestations, patients with PsA frequently exhibit alterations in lipid metabolism, contributing to an increased risk of cardiovascular disease. Dyslipidemia in PsA arises from multiple mechanisms, including systemic inflammation, insulin resistance, and imbalances in adipokines such as leptin, adiponectin, and resistin. A structured literature search was conducted in PubMed, Scopus, and Web of Science to identify relevant studies on lipid metabolism in psoriatic arthritis, and the evidence was synthesized narratively. PsA is also commonly associated with obesity and metabolic syndrome, further exacerbating dyslipidemia and cardiovascular risk. Interventions including weight loss, lifestyle modification, and anti-inflammatory treatments have been shown to improve lipid profiles and clinical outcomes. This review provides a comprehensive overview of current knowledge on altered lipid metabolism in PsA, highlighting underlying mechanisms, clinical implications, and therapeutic strategies to reduce cardiovascular risk. Full article

Cardiovascular diseases are the primary causes of mortality worldwide, often characterized by subtle onset and acute progression. Traditional ECG electrodes may cause skin irritation, limiting routine monitoring and early risk assessment. Relying on the advantages of non-contact monitoring, millimeter-wave radar-based cardiac monitoring combined with deep learning has become a popular research direction recently. To overcome the poor generalization of methods trained from single-source datasets, this study designed seven experimental scenarios covering wakefulness and sleep. A novel deep learning network consisting of encoder and decoder structures named PMG-SATNet was proposed. The encoder comprises a parallel multi-scale feature extraction module and a global temporal relationship modeling module to capture fine-grained local patterns and long-range dependencies. The decoder employs a temporal convolutional network augmented with a spectral attention mechanism to emphasize clinically relevant ECG frequency bands and suppress respiration and body motion interference. After being validated on the self-built dataset, PMG-SATNet outperformed baseline models in terms of Pearson correlation coefficient and root mean square error, with an improvement of 3.3% and 3.8%, and 16.4% and 23.8%, respectively. The validation results imply that PMG-SATNet is capable of recovering ECG signals from millimeter-wave radar-derived chest vibrations with high fidelity and can potentially be implemented in real-life cardiac health monitoring. Full article

Astragalus species have been used in traditional medicine for the treatment of various conditions, and they have recently been used to treat dermatological diseases. Health benefits of Astragalus extracts, especially Astragalus membranaceus Fisch. ex Bunge (synonym of Astragalus mongholicus Bunge), result from the multitude of secondary metabolites identified in their genus, including saponins, flavonoids and polysaccharides. Astragalus species, traditionally valued for their systemic medicinal properties, are increasingly recognized as potent sources of ingredients for the cosmeceutical industry. While A. membranaceus remains the most prominent representative, this review explores the broader genus as an emerging reservoir of bioactive secondary metabolites. For this purpose, current publications regarding the topical effects of Astragalus species in the treatment of dermatological diseases were collected. Several Astragalus extracts and their compounds have been shown to display biological activities with skin rejuvenating, photoprotective and antimicrobial properties, wound-healing activity, and therapeutic effects on atopic dermatitis and alopecia. However, these articles have limitations because of their use of non-human mammals and the short duration of trials, and future research is needed to fill these gaps. Full article

Background: Prostate cancer (PCa) imposes a substantial global health burden, with robot-assisted radical prostatectomy (RARP) established as the gold standard for localized disease. While da Vinci^® Xi maintains market dominance, Toumai^® MT-1000 offers a potentially cost-competitive alternative lacking prospective validation. Objective: To evaluate perioperative safety, oncologic quality (primary endpoint: positive surgical margins), early functional recovery (continence), and surgeon learning curve between Toumai^® MT-1000 (T-RARP) and da Vinci^® Xi RARP (DV-RARP) performed in high-volume European practice. Materials and Methods: This is a prospective single-center comparative study carried out at Policlinico Gemelli, Rome (May–November 2025), enrolling 80 patients with localized or locally advanced PCa, elected for radical prostatectomy and casually allocated to receive surgery with Toumai or the da Vinci robotic platform. The primary endpoint was the comparison of positive surgical margin (PSM) rates. Secondary endpoints included the comparison of operative time (skin-to-skin), estimated blood loss, length of hospital stay, 45-day postop outcomes, specifically Clavien–Dindo complications, urinary continence recovery (0–1 pad/day), and IIEF-5 scores. Learning curve was evaluated through the cumulative summation (CUSUM) analysis of operative times and linear regression of operative times (n = 80 cases). The analyses used STATA 19 with two-sided tests at p < 0.05 significance. Results: Baseline characteristics showed balance between cohorts (p > 0.05 for most covariates). Perioperative outcomes proved equivalent: median operative time (OT) was 192.5 min (IQR 165–230) for Toumai^® versus 183.5 min (IQR 147–225) for da Vinci^® Xi (p = 0.38); estimated blood loss (EBL) was 150 mL in both groups (p = 0.87); length of hospital stay (LOS) was 2 days in both groups (p = 0.92). PSM rates were identical at 17.5% (p = 0.79). Continence recovery reached 72.5% versus 80% (p = 0.43). Complications (Clavien–Dindo ≥ II) occurred in 7.5% versus 12.5% of cases (p = 0.45). The CUSUM analysis demonstrated operative time proficiency after only four procedures; operative time regression showed no significant trend (p = 0.38). Conclusions: Toumai^® MT-1000 demonstrates similar performance to da Vinci^® Xi across different RARP quality metrics, with no detectable learning curve for surgeons previously experienced with da Vinci. These findings support a safe integration of cost-effective platforms into clinical practice, pending multicenter randomized confirmation. Full article

Skin cancer represents a significant public health challenge, necessitating early detection and timely treatment for optimal management. Timely and accurate evaluation of skin lesions is crucial, as delays can lead to more severe outcomes. However, identifying skin lesions accurately can be challenging due to differences in color, shape, and the various types of imaging equipment used for diagnosis. While recent studies have demonstrated the potential of ensemble convolutional neural networks (CNNs) for early diagnosis of skin disorders, these models are often too large and inefficient for processing contextual information. Although lightweight networks like MobileNetV3 and EfficientNet have been developed to reduce parameters and enable deep neural networks on mobile devices, their performance is limited by inadequate feature representation depth. To mitigate these limitations, we propose a new hybrid attention dual-stream deep learning model for skin lesion detection. Our model uses one training process to preprocess the images and splits the task into two branches. Each branch extracts different features using multi-stage and multi-branch attention techniques, improving the model’s ability to detect skin lesions accurately. The first branch processes the original image using a convolutional layer integrated with three novel attention modules: Enhanced Separable Depthwise Convolution (SCAttn), stage attention, and branch attention. The second branch utilizes Contrast Limited Adaptive Histogram Equalization (CLAHE) to enhance the input image, improving local contrast and revealing finer details. The integration of CLAHE with SCAttn modules leverages enhanced local contrast to capture more nuanced features while maintaining computational efficiency. A classification module receives the concatenated hierarchical characteristics that were taken from both branches. Utilizing the PAD2020 and ISIC 2019 datasets, we assessed the proposed model and obtained an accuracy rate of 98.59% for PAD2020, surpassing the state-of-the-art performance by 2%, and stable performance accuracy for the ISIC 2019 dataset. This illustrates how well the model can integrate several attention mechanisms and feature enhancement methods, providing a reliable and effective means of detecting skin cancer. Full article

A history of invasive mold disease (IMD) often delays or contraindicates allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. Given the limited data on pediatric patients with pre-allo-HSCT IMD, we aimed to describe the management and clinical outcomes of a cohort of children with IMD prior to allo-HSCT through day +100 post-transplantation. Between 2021 and 2024, ten pediatric patients were identified with proven or probable IMD. Their median age was 8.5 years. The most common pathogens were Aspergillus (n = 5) and Fusarium (n = 4). Infections most frequently involved the lungs followed by paranasal sinuses, bloodstream, liver, and skin. All patients demonstrated clinical improvement before transplantation, and by day +100 post-HSCT, no IMD relapses or infection-related mortality were observed. These findings suggest that complete radiologic or clinical resolution is not a prerequisite for proceeding with transplantation. Recent IMD should not be considered an absolute contraindication to urgent allo-HSCT when clinical improvement is evident, as transplantation facilitates immune reconstitution necessary for definitive infection control. Full article

Objectives: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease that significantly impairs patients’ quality of life, especially in its moderate to severe forms. Traditional treatments, including antibiotics, hormonal therapies, and surgery, often fail to provide long-term relief in such cases. This study aims to explore the role of radiotherapy, particularly with the use of 3D printing technology to create personalized boluses and applicators, as an adjunctive treatment for refractory HS. A systematic review of published studies was conducted to assess the efficacy of radiotherapy in managing HS, with a specific focus on studies using 3D printing technology to create customized boluses and applicators. Methods: Publications from databases such as PubMed, Scopus, and Google Scholar were analyzed for studies detailing radiotherapy techniques, dosing regimens, and the use of 3D-printed devices in HS treatment. The studies selected included those employing both external beam radiotherapy and brachytherapy, with particular emphasis on patient outcomes and adverse effects. Results: The reviewed studies highlighted a growing body of evidence supporting the use of radiotherapy for HS, especially in severe or treatment-resistant cases. The use of 3D-printed boluses and applicators in radiotherapy demonstrated significant improvements in treatment precision and patient comfort. Personalized treatment plans allowed for more accurate dose distribution, minimized air gaps, and reduced exposure of healthy tissue. No major long-term toxicity was reported across the majority of studies. Conclusions: Radiotherapy, particularly when combined with 3D printing technology, presents a promising treatment option for patients with severe or refractory HS. Customizable boluses and applicators enhance the precision of radiotherapy by conforming to irregular skin surfaces, thereby improving dose conformity and reducing side effects. Despite the positive results, further research is needed to assess the long-term safety and clinical feasibility of this approach. The integration of 3D printing in radiotherapy could significantly improve treatment outcomes, offering a more personalized and effective therapeutic option for HS patients. Full article