Search Results (458)

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which gut–skin axis dysregulation is increasingly implicated. We conducted a prospective pilot study to describe the clinical evolution of pediatric AD following individualized, stool-guided microbiota-targeted therapy and to explore whether baseline dysbiosis markers predict outcomes beyond baseline disease severity. Methods: Twenty-one children with AD and laboratory-confirmed gut dysbiosis were enrolled consecutively at a tertiary pediatric center in Romania in a single-arm prospective pilot study. Gut microbiota was assessed using targeted culture-based stool analysis, generating a Flora Index and a binary High Putrefaction Flora classification. Individualized treatment consisted of strain-specific probiotics, prebiotics, and antifungals when indicated. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) at baseline, 30 days, and 90 days. Longitudinal changes were evaluated using repeated-measures ANOVA and hierarchical regression models. Results: High Putrefaction Flora was present in 71.4% of participants. Mean POEM decreased from 14.67 ± 5.22 at baseline to 7.10 ± 3.82 at 90 days, while mean SCORAD decreased from 41.66 ± 15.28 to 17.93 ± 11.68 (both p < 0.001). Approximately 76% of participants achieved a ≥50% reduction in POEM, and 71% achieved a ≥50% reduction in SCORAD. Individualized microbiota-targeted therapy was associated with substantial improvements in both clinical and patient-reported disease severity over the 90-day follow-up. Although children with High Putrefaction Flora exhibited higher disease severity scores in unadjusted analyses, baseline disease severity was the only significant predictor of 90-day outcomes. The Flora Index provided no independent explanatory value. Conclusions: In this exploratory single-arm pilot study, individualized microbiota-targeted therapy was associated with substantial and clinically meaningful improvement in AD severity over 90 days. Dysbiosis markers were associated with disease burden but did not independently predict outcomes, suggesting that they may function primarily as indicators of baseline severity rather than prognostic biomarkers. Because of the uncontrolled study design, causal inferences regarding treatment effects cannot be made, and these findings should be considered hypothesis-generating. Adequately powered randomized controlled trials are required to determine the efficacy of individualized microbiota-targeted interventions in pediatric atopic dermatitis. Full article

Anti-obesity medications (AOMs), led by the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have produced substantial weight reduction and growing signals of benefit that extend well beyond adiposity. These agents are now discussed in relation to longevity and aesthetic medicine, raising the question of whether their effects reach ageing biology and appearance. This narrative review (PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, and Clinical trial registries; January 2010–June 2026) integrates mechanistic studies, randomised cardiovascular and renal outcome trials, ageing-biomarker analyses, body-composition data, and patient-facing aesthetic phenomena. The evidence indicates that AOMs reduce major cardiovascular events, slow kidney and liver disease progression, and lower all-cause mortality in selected populations; exploratory proteomic and epigenetic analyses further suggest effects partly independent of weight loss, though these do not establish slowed ageing. Newer multi-receptor agents act with greater metabolic specificity: glucagon-containing agents such as survodutide and the triple agonist retatrutide preferentially reduce visceral and hepatic fat (liver-fat reductions of roughly 60–80% in places), a quality of weight loss arguably more relevant to healthspan than its quantity. Concurrently, rapid large-magnitude weight loss drives soft-tissue and appearance changes colloquially termed “Ozempic face” and “Ozempic body”, alongside accelerated skin laxity and loss of lean mass, the latter tempered by data showing lean-loss proportions comparable to established agents. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which type 2 immune activation, epidermal barrier dysfunction, microbial dysbiosis, and neurosensory pathways interact to sustain disease activity and symptom burden. Despite major advances with biologics and Janus kinase inhibitors, residual xerosis, pruritus, sleep disturbance, and barrier fragility may persist in otherwise controlled patients. This narrative review evaluates balneotherapy as adjunctive supportive care in AD, focusing on skin barrier function, microbiome-related effects, pruritus, and clinical integration. A narrative literature review was conducted using PubMed/MEDLINE, Ovid, and Scopus from database inception to 31 December 2025. Search terms addressed AD, type 2 inflammation, skin barrier dysfunction, transepidermal water loss, pruritus, microbiome dysbiosis, thermal spring water, spa therapy, seawater therapy, Dead Sea climatotherapy, hydrotherapy, and balneophototherapy. Clinical, mechanistic, translational, and methodological studies were considered. Available evidence suggests that water-based interventions may improve selected patient-centred outcomes, particularly xerosis-related discomfort, pruritus, sleep impairment, quality of life, and global severity scores. Thermal spring water programmes, Dead Sea climatotherapy, seawater-based approaches, and balneophototherapy differ substantially in exposure characteristics, co-interventions, and outcome reporting. Objective endpoints such as transepidermal water loss, skin hydration, tape stripping biomarkers, and microbiome profiling may help clarify biological plausibility, although current evidence is limited by heterogeneity, short follow-up, and difficulty isolating water-specific effects. Balneotherapy should be positioned as an adjunctive, supportive intervention rather than an alternative to evidence-based anti-inflammatory therapy in AD, particularly for selected patients with persistent barrier- and symptom-dominant residual burden. Full article

Eosinophils are tissue-adapted granulocytes with important roles in host defense, immune regulation, barrier responses, and inflammatory disease. Beyond classical degranulation, activated eosinophils can release eosinophil extracellular traps (EETs), extracellular DNA and protein structures that arise through cytolytic nuclear EETosis or rapid mitochondrial DNA (mtDNA) release. These traps may contribute to host protection by immobilizing pathogens and concentrating eosinophil granule proteins at sites of mucosal or tissue inflammation. However, when EET formation is excessive, persistent, or insufficiently cleared, the same structures may promote epithelial injury, mucus viscosity, thromboinflammation, tissue remodeling, fibrosis, and chronic eosinophilic inflammation. This review summarizes the cellular mechanisms, structural organization, inducing stimuli, and disease relevance of EETs. Particular attention is given to infectious settings, eosinophilic airway and middle-ear disease, systemic vasculitic and hypereosinophilic disorders, inflammatory skin and ocular diseases, eosinophilic gastrointestinal disease, and cancer. Current evidence indicates that EETs should be interpreted as context-dependent eosinophil effector structures with dual biological potential. Although their mechanistic relevance is increasingly recognized, further histological, functional, and clinical validation is needed before EETs can be established as reliable biomarkers or therapeutic targets. Full article

Systemic sclerosis (SSc) is a rare, clinically heterogeneous connective tissue disease defined by the triad of autoimmunity, microvasculopathy, and fibrosis of the skin and internal organs. Among the immune effectors implicated in SSc, B cells have moved from being regarded mainly as the source of disease-defining autoantibodies to being recognized as multifunctional drivers of disease through antibody-independent mechanisms. This review summarizes current understanding of B-cell biology in SSc across three domains. First, we consider the classical role of B cells as antibody-producing cells, including the diagnostic and prognostic value of SSc-specific autoantibodies, the evidence for polyclonal B-cell activation and altered B-cell homeostasis, and the contested question of autoantibody pathogenicity. Second, we examine antibody-independent functions, focusing on cytokine production by effector and regulatory B-cell subsets, the B-cell-activating factor (BAFF) axis, antigen presentation, and T-cell co-stimulation, together with the imbalance between pro-inflammatory effector B cells and interleukin (IL)-10-producing regulatory B cells that characterizes active disease. Third, we review B cells as therapeutic targets, from the rituximab experience—including the randomized DESIRES trial and its open-label extension—through anti-BAFF strategies to the emerging use of CD19-directed chimeric antigen receptor (CAR) T-cell and CAR-natural killer (NK) cell therapies that achieve deep, durable B-cell depletion. We conclude by highlighting unresolved questions, including patient selection, the balance between depleting pathogenic and protective B-cell subsets, biomarker development, and the long-term safety of deep B-cell depletion. A B-cell-centered view of SSc pathogenesis provides a coherent framework that links autoimmunity to fibrosis and is increasingly translatable into the clinic. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction, immune dysregulation, and marked clinical heterogeneity. Growing evidence implicates the gut microbiome in AD-related pathways through microbial metabolites, intestinal barrier function, and systemic immune signaling. This narrative review synthesizes current evidence on gut microbial alterations in AD, with particular attention to short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, intestinal permeability, gut–skin microbiome interactions, and microbiota-targeted interventions. Human studies have reported associations between AD and altered abundance of selected microbial taxa, metabolite profiles, and markers of intestinal barrier dysfunction, whereas animal and in vitro studies provide complementary mechanistic evidence. However, findings remain heterogeneous across age groups, disease phenotypes, geographic populations, analytical platforms, and treatment exposures, and causality is incompletely established. Probiotic and synbiotic interventions have shown strain-specific and context-dependent effects, while postbiotics, fecal microbiota transplantation, washed microbiota transplantation, and metabolite-directed approaches remain investigational. AI-assisted multi-omics methods may improve biological stratification and hypothesis generation, but current applications are limited by small sample sizes, cohort heterogeneity, overfitting, insufficient external validation, and limited clinical implementation. Current evidence therefore supports the gut microbiome as a mechanistically plausible contributor, potential biomarker, and therapeutic target in AD while underscoring the need for longitudinal, phenotype-aware, and externally validated studies before routine clinical translation. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with a well- documented prodromal phase during which non-motor symptoms appear years before motor onset. Seborrheic dermatitis (SD) is a chronic inflammatory skin disease that is significantly more prevalent in PD patients than in the general population. The biological mechanisms underlying this association have not been integrated into a single framework. Objectives: This narrative review aims to synthesise the available evidence on the molecular, genetic, and pathophysiological mechanisms linking SD and PD. Methods: A literature search was conducted across PubMed/MEDLINE, Scopus and ScienceDirect, supplemented by manual searches in OMIM and GeneCards. Results: Four major biological links between SD and PD have been proposed. First, alpha-synuclein deposits are detectable in cutaneous nerve fibres and autonomic fibres innervating sebaceous glands in PD patients and their pattern has been associated with disease subtype and progression. Second, dysfunction in ceramide and sphingolipid metabolism, associated with variants in GBA1, LRRK2, and ZNF750, has been linked to impaired lysosomal function and skin barrier integrity in both brain and skin tissue. Third, Malassezia, a commonly associated organism and possible trigger in susceptible hosts, produces metabolites that activate neuroinflammatory pathways relevant to PD and PD patients show altered Malassezia species composition on their skin. Fourth, NLRP3 inflammasome activation, which can be triggered by ceramide accumulation and fungal metabolites, has been proposed as a shared inflammatory mechanism that may operate in both keratinocytes and dopaminergic neurons. Conclusions: SD and PD appear to share overlapping genetic, lipidomic, microbial, and neuroinflammatory features. These associations are consistent with, but do not yet prove, a common pathological basis rather than a coincidental one. SD may therefore represent a potential prodromal feature or risk marker of PD. Future research should examine whether targeted intervention in high-risk SD patients can delay or modify PD onset. Full article

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease involving barrier dysfunction, pruritus, and immune dysregulation, and microbial-based interventions are being explored as supportive approaches. This study first conducted an exploratory pilot model-development experiment to characterize DNCB-induced dermatitis-like inflammation and subsequently compared oral live Lactobacillus, heat-killed Lactobacillus (paraprobiotics), and a combined live/heat-killed formulation after disease induction. Methods: Male BALB/c mice received repeated topical DNCB exposure followed by 21 days of oral intervention. Outcomes included gross lesion scores, cumulative scratching time, ear and spleen indices, histopathology, qualitative mast-cell staining in the therapeutic experiment, and serum IgE, IL-4, and IFN-γ. Longitudinal gross scores were reanalyzed using generalized estimating equations with group, time, and group-by-time interaction. Results: After Holm correction, the mixed formulation showed a lower left-ear erythema score than placebo at Week 2, whereas no other intervention-versus-placebo gross-score comparison remained significant. Paraprobiotic and mixed formulations reduced spleen weight, but histopathological and serum biomarker responses were variable. Conclusions: These findings indicate partial, endpoint-dependent effects of live and heat-killed Lactobacillus formulations in DNCB-induced dermatitis-like inflammation. Full article

Pruritus is a debilitating symptom frequently affecting patients with cholestatic liver disease, often resistant to conventional antipruritic therapies. The pathogenesis of cholestatic pruritus (CP) is multifactorial, implicating not only bile acids but also a complex array of other potential pruritogenic mediators and neural signaling pathways. Identification of the exact pruritogen has been elusive, and gaps remain in understanding the pathogenesis of pruritus, so developing targeted treatments is critical. The stratum corneum (SC), the outermost lipid-rich layer of the skin, may act as a reservoir for circulating pruritogens, offering a novel window to explore the pathogenesis of CP. Recent advancements in lipidomics and non-invasive tape stripping have enabled detailed profiling of SC lipid alterations in disease states. In this review, we synthesize the current understanding of CP and its candidate pruritogens and describe state-of-the-art approaches for SC lipid analysis, combining tape stripping to sample the skin surface with mass spectrometry-based lipidomics. Finally, we summarize cutaneous molecular findings and discuss how these techniques are facilitating biomarker discovery and informing therapeutic development. This review discusses the paradigm shift from a single-molecule perspective to a more integrated view of CP as a product of complex mediator interactions and highlights the potential of SC profiling to uncover novel targets for intervention strategies. Full article

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the predominant cutaneous T-cell lymphomas. Although malignant T cells in MF/SS overexpress CCR4 and respond to the anti-CCR4 antibody mogamulizumab, skin response rates vary. We hypothesized that immune components within the tumor microenvironment contribute to differential outcomes. Methods: Imaging mass cytometry with a 37-antibody panel was used to characterize immune and structural elements in FFPE tissues from sixteen MF/SS patients (6 MF, 10 SS) treated with Mogamulizumab, including seven skin responders and nine non-responders. Single-cell phenotyping and spatial analyses were performed using the Visiopharm^® Phenoplex™ platform, with supervision. Results: We identified 68,974 cells pre-treatment and 58,852 cells post-treatment. Malignant CD4⁺ T cells showed reduced baseline CD27, CD103, CD25, and ICOS expression compared with non-malignant CD4⁺ cells. Baseline MF lesions were enriched for IL-13⁺ and CD103⁺ malignant T cells, whereas SS lesions contained higher proportions of CD27⁺ and LAG3⁺ cells. IL 13⁺ malignant cells decreased after treatment, most prominently in MF. Myeloid profiles differed by disease and response: MF lesions exhibited baseline enrichment of M1-like macrophages (CD86⁺, HLA-DR⁺), while SS lesions were predominantly M2-polarized macrophages (CD163⁺, CD206⁺). Responders showed increased M1-like macrophages, whereas non-responders displayed reduced M1-features. An increase in DC3-like cells was observed in non-responders following treatment. Conclusions: This single-cell spatial atlas reveals shared and subtype-specific immune features in MF/SS. Th2-skewed malignant T-cell status and myeloid polarization correlate with clinical response, supporting their potential as spatial biomarkers for patient stratification in mogamulizumab therapy. Full article

Leprosy presents a broad clinical–immunological spectrum, whose heterogeneity challenges early diagnosis and disease stratification. Metabolomic approaches have emerged as promising tools for identifying potential biomarkers associated with the disease’s pathophysiology. This study aimed to investigate metabolic profiles associated with the different clinical forms of leprosy using untargeted metabolomics in formalin-fixed paraffin-embedded (FFPE) tissue samples. A retrospective cross-sectional study was conducted with 55 patients classified according to the Ridley–Jopling spectrum. Metabolites were extracted from FFPE skin biopsies and analyzed by liquid chromatography–mass spectrometry (LC-MS). From 908 metabolites initially detected, 27 were retained after frequency filtering. Six metabolites ultimately met the criteria of one-way analysis of variance (ANOVA, p < 0.05) and fold-change (FC ≥ 2.0) for differential expression, while N-stearoyl tryptophan was identified as an additional candidate metabolite based on its contribution to multivariate group discrimination. These included 11-hydroperoxy-H4-neuroprostane, which showed a specific association with bacterial load, and the Gly-Pro-Lys tripeptide, which correlated with markers of infection progression. Metabolomics applied to FFPE samples proved feasible for discriminating the clinical spectrum of leprosy and annotating signatures associated with immune response. This approach represents an innovative strategy for exploratory biomarker discovery using archived histopathological samples in translational research. Full article

Background: Novel Sézary syndrome (SS) biomarker genes identified previously through transcription profiling were examined for changes in expression after mogamulizumab treatment. Incorporating new biomarkers for measuring response to disease would improve clinical care. Objective: To assess novel SS biomarker and cytokine genes in patients treated with mogamulizumab with clinical response, blood response, and immunologic parameters. Methods: We performed a real-world case–control and case–case study analyzing the expression of SS biomarker genes in peripheral blood mononuclear cells (PBMCs) from six SS patients treated with mogamulizumab using qRT-PCR. Results: We demonstrated a reduced expression of SS biomarker genes in PBMCs of SS patients following mogamulizumab therapy. In our cohort, five of the SS biomarker genes (PLS3, TWIST1, KCNK1, DNM3 and TOX) showed statistically consistent high expression compared to normal PBMCs at baseline. After treatment with mogamalizumab, these five SS biomarkers showed significant correlations with skin response (p < 0.05) and three (TOX, TCRL3 and DNM3) with blood response (p < 0.05). A decrease in GATA3 expression correlated to an improvement in skin severity, and STAT4 inversely correlated to Sézary cell decrease (p < 0.05). Two cytokine genes, IL4 and IFNG, reflective of an immune response that is abnormal in SS, showed a trend to normalized expression with IL-4 decreasing and IFNG increasing after treatment. Limitations: This was a real-world study of patients who failed prior treatments, with a small sample size and variable timing between patient sample collection. Conclusions: Unique SS biomarker, cytokine and T cell transcription factor genes are valuable in assessing molecular and immune responses following treatment. Full article

Background: Food allergy is a heterogeneous pediatric disease involving IgE-mediated, non-IgE-mediated, and mixed immune mechanisms, with manifestations ranging from mild symptoms to life-threatening anaphylaxis. Current diagnostic tools, including clinical history, skin prick testing, serum-specific IgE measurement, and oral food challenge, have limitations in specificity, invasiveness, prognostic value, and ability to guide personalized management. Methods: This narrative review summarizes emerging biomarkers in pediatric food allergy and evaluates their diagnostic, prognostic, predictive, and therapeutic potential. A literature search was conducted in PubMed/MEDLINE and Cochrane Central for English-language studies published between December 2015 and March 2026. Eligible studies included original clinical or translational research involving children aged 0–18 years and assessing functional cellular assays, epithelial barrier markers, intestinal permeability, gut microbiota, metabolomics, transcriptomics, proteomics, epigenetics, and immune biomarkers. Findings were synthesized qualitatively according to biomarker category and biological function. Results: Functional cellular biomarkers, particularly the basophil activation test, show the greatest translational readiness, with high diagnostic specificity, utility in reaction threshold and severity assessment, and potential value for monitoring oral immunotherapy. Biomarkers of epithelial barrier dysfunction, including zonulin, tight junction proteins, epithelial injury markers, filaggrin variants, and epithelial-derived cytokines, provide mechanistic insight into allergic sensitization and gastrointestinal phenotypes but remain insufficiently validated. Microbiota-derived, metabolomic, transcriptomic, proteomic, epigenetic, and integrated multi-omics approaches offer promising tools for risk prediction, tolerance monitoring, endotype identification, and precision medicine. Conclusions: Emerging biomarkers may improve diagnosis, risk stratification, therapeutic monitoring, and personalized care in pediatric food allergy. However, standardized assays, large longitudinal pediatric studies, and external validation are required before routine clinical implementation. Full article

Nimotuzumab is a humanized anti-EGFR monoclonal antibody with a unique pharmacodynamic profile characterized by intermediate affinity and bivalent binding dependence, enabling density-selective tumor targeting while sparing normal tissues from the severe skin rash and other toxicities common to EGFR inhibitors. Since its first approval in 2002, nimotuzumab has been registered for eight cancer indications. Unlike conventional fixed-dose schedules, emerging evidence supports prolonged administration beyond initial combination therapy. This review summarizes clinical data from pancreatic cancer, esophageal cancer, high-grade glioma, pediatric diffuse intrinsic pontine glioma, head and neck squamous cell carcinoma, nasopharyngeal cancer and other solid tumors, showing that extended nimotuzumab exposure, often as maintenance monotherapy, may prolong overall survival, progression-free survival, and disease control compared to limited cycles. Despite heterogeneity in tumor types and treatment regimens, maintenance nimotuzumab was consistently associated with better results, particularly in terms of overall survival. Notably, significant survival benefits were observed in locally advanced SCCHN (24.9 vs. 12.5 months) and esophageal cancer (15.9 vs. 8.1 months) across independent clinical trials. Mechanistically, nimotuzumab exerts direct cytostatic effects via G1 arrest, potent anti-angiogenic activity through VEGF downregulation, indirect pro-apoptotic effects, and broad immunomodulation including ADCC, NK-DC cross-talk, EGFR-specific CD8+ T cell priming, upregulation of HLA class I, and favorable regulation of regulatory T cells. Its density-selective binding reduces selective pressure for acquired resistance. Future research priorities should include prospective randomized trials specifically evaluating maintenance strategies, biomarker-driven patient selection, the molecular characterization of resistance mechanisms, integration with immunotherapy and modern combination regimens, and the development of next-generation platforms, including antibody–drug conjugates and multi-specific constructs. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by substantial clinical and immunological heterogeneity. Once considered primarily a disorder of epidermal barrier dysfunction, AD is now recognized as a complex systemic inflammatory condition involving dysregulated immune responses, epithelial-derived signaling, neuroimmune interactions, and diverse molecular endotypes. Advances in molecular immunology have substantially improved understanding of the cytokine networks underlying disease pathogenesis and have accelerated the transition toward precision medicine approaches in AD. This narrative review summarizes current evidence regarding the immunopathogenesis of AD, focusing on the interplay between classical and emerging cytokine pathways, biomarker development, and recent therapeutic innovations. While interleukin (IL)-4 and IL-13 remain central drivers of type 2 inflammation and barrier impairment, additional mediators including IL-31, IL-33, IL-22, thymic stromal lymphopoietin (TSLP), and OX40/OX40L signaling, and the emerging Th9/IL-9 axis contribute to chronic inflammation, neuroimmune activation, epidermal remodeling, pruritus, and disease heterogeneity. Comparative evaluation of these pathways supports the identification of distinct immunological endotypes relevant to disease stratification and targeted therapy. The review further discusses current and emerging biomarkers associated with disease severity, therapeutic responsiveness, and inflammatory profiling, including cytokine signatures, serum biomarkers, and transcriptomic approaches. Recent advances in biologic therapies, Janus kinase (JAK) inhibitors, and novel cytokine-targeted interventions are discussed within the context of a precision medicine framework integrating immunological profiling, molecular endotyping, and mechanism-based therapeutic innovation. Continued advances in biomarker discovery, multi-omics technologies, and predictive therapeutic algorithms are expected to further refine disease stratification and support increasingly individualized management strategies for patients with AD. Full article