Search Results (838)

Vaccination ranks among the most consequential interventions in medicine, yet cold-chain dependence, sharps hazards, needle phobia, and reliance on trained vaccinators limit coverage where vaccine-preventable mortality is highest. Microneedle patches deposit antigen into the antigen-presenting-cell-rich epidermis and upper dermis through projections that penetrate the stratum corneum without reaching dermal nociceptors. Such targeting yields immunogenicity matching or exceeding intramuscular injection at a fraction of the antigen mass, with dose-sparing up to six-fold recorded for influenza, polio, and SARS-CoV-2 antigens. Solid-state formulation converts that immunological advantage into a logistical one, since polymeric matrices preserve potency for as long as two years at ambient temperature, removing the refrigeration infrastructure that consumes significant delivery cost. Six microneedle types have reached preclinical or clinical maturity, with dissolving microneedle patches the most advanced. Two trials provide the clinical evidence: a Phase I influenza study showing non-inferior antibody responses and successful self-application, and a Phase I/II measles–rubella trial in The Gambia reaching 93% measles and 100% rubella seroconversion in infants without related serious adverse events. Engineering advances currently include an automated printer producing thermostable mRNA–lipid nanoparticle patches that retain bioactivity for six months at ambient temperature, the first intradermal self-amplifying RNA patch, and quantum-dot on-body immunization records. Sterility assurance, dose uniformity, nucleic acid integrity within solid matrices, and fragmented regulatory guidance remain the challenging obstacles, alongside a clinical pipeline concentrated on few antigens. This review integrates the mechanistic, materials, manufacturing, clinical, regulatory, and global health dimensions of the field to guide translation and equitable deployment. Full article

Skin is the outermost layer which covers all organs of the body. Skin can be divided into three layers, including epidermis, dermis and hypodermis. Similarly to many organs of the body, skin also experiences biological process that could not resist aging. There are the following two types of human skin aging: endogenous and exogenous. Endogenous aging involves a series of physiological changes that gradually occur over time and are influenced by genes and hormones. In contrast, extrinsic aging (or exogenous aging), also known as photoaging, involves significant structural and functional changes due to external factors, mainly due to lack of sun protection, smoking, air pollution, lifestyle, etc. Skin aging not only affects the appearance but also makes the skin more sensitive to geriatric skin diseases. In order to treat geriatric skin disease effectively and appropriately, it is crucial to study skin aging from a clinical and histological perspective. Full article

Skin aging is a multifactorial process involving structural and functional changes in the dermis. In recent years, the treatment of age-related skin changes in the face, neck, and décolleté has become a growing focus in the fields of esthetic medicine and dermatology. The increasing demand for natural, youthful results without surgical intervention or prolonged downtime has led to the development and widespread application of minimally invasive energy-based technologies, such as High-Intensity Focused Ultrasound (HIFU) and Radiofrequency (RF). The aim of this review is to summarize current evidence regarding the mechanisms of action, clinical efficacy, and safety of HIFU and RF, as well as their combined applications in skin rejuvenation. Relevant studies were selected based on their scientific quality and relevance to the topic. Current evidence indicates that both HIFU and RF promote collagen remodeling and dermal tightening through different energy-delivery mechanisms. Comparative studies suggest that their combined use may enhance esthetic outcomes and improve patient satisfaction. Overall, these technologies represent innovative, non-surgical approaches for facial, neck, and décolleté rejuvenation. Full article

Reconstructive surgery still faces various challenges when dealing with the reconstruction of complex skin defects, regardless of their origin (e.g., trauma, burns). Split-thickness autologous skin grafts remain the gold standard; however, this technique comes with several limitations, including donor site morbidity, infection, and scarring. Since extensive research on conventional techniques has not provided sufficient long-term results, there has been a shift toward dermal substitutes made from regenerative biomaterials that can aid wound management and support tissue restoration. This structured review will introduce the challenges posed by complex skin defects, the limitations of autologous skin grafts and conventional reconstruction techniques, and the emerging field of dermal substitutes and biomimetic scaffolds. Moreover, the native dermis is presented as a blueprint for biomimetic scaffold design, along with key principles to consider when engineering a dermal scaffold, from architecture and porosity to angiogenic potential. A critical examination of the main classes of available dermal substitutes and their clinical performance is conducted, highlighting their limitations and the translational gaps in current evidence. Although the current pool of biomaterials still faces challenges in accurately mimicking the properties and architecture of natural skin, future perspectives offer promising alternatives that could overcome these limitations. Full article

Di-(2-ethylhexyl) phthalate (DEHP), a ubiquitous environmental plasticizer, has been increasingly linked to the exacerbation of inflammatory skin conditions, especially psoriasis. However, the mechanisms and effective therapeutic strategies targeting DEHP-aggravated psoriasis remain elusive. We integrated network toxicology, network pharmacology, and molecular docking to explore the targets of DEHP-exacerbated psoriasis and the protective effects of shikonin (SH). These findings were validated in a DEHP/IMQ-induced mouse model using a novel shikonin nanoparticle (SH-NP) that overcomes SH’s inherent hydrophobicity. Computational analyses revealed that SH counteracts DEHP skin toxicity through a multi-target network, identifying the p38 mitogen-activated protein kinase (p38 MAPK), TNF, IL-1β, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinases 2 and 9 (MMP2/9) as core therapeutic nodes. Molecular docking verified this network, revealing robust binding between SH and key targets with binding energies ranging from −6.0 to −7.8 kcal/mol, consistently outperforming DEHP. In vivo experiments demonstrated that topical application of SH-NP significantly ameliorated macroscopic skin injury and reduced PASI scores. Mechanistically, SH-NP effectively reversed the DEHP-exacerbated inflammatory microenvironment by decreasing macrophage and mast cell infiltration in the dermis, reducing pro-inflammatory cytokine levels, and inhibiting the phosphorylation of p38 MAPK. Furthermore, SH-NP treatment successfully suppressed keratinocyte hyperproliferation, as evidenced by downregulated PCNA expression and reduced epidermal thickness. SH-NPs also markedly downregulated the elevated levels of MMP2/9 in mice, thereby mitigating collagen degradation and maintaining dermal matrix integrity. This study shows that SH-NPs alleviate DEHP-aggravated psoriasis by suppressing local inflammation, keratinocyte hyperproliferation, and collagen degradation, offering a targeted nanostrategy for environmentally exacerbated skin diseases. Full article

Background/Objectives: Cervical integument aging is a complex, multifactorial process characterized by thinning dermis, loss of elasticity, and platysmal band prominence. Multimodal treatments targeting these distinct anatomical layers simultaneously remain limited. This study aimed to evaluate the clinical efficacy, safety, and rejuvenation potential of the STIIM UP Protocol, a single-session treatment combining calcium hydroxyapatite (CaHA), hyaluronic acid (HA), and botulinum toxin type A (BoNT-A) for neck rejuvenation. Methods: This prospective, open-label, exploratory clinical study enrolled 13 healthy women (n = 13) presenting with cervical laxity. The STIIM UP suspension was delivered bilaterally into the subdermal plane of the anterior neck region using a retro-injection fanning technique with a 22G cannula at Day 0 (D0). Evaluated outcomes included the IBSA Neck Grading Scale, Global Aesthetic Improvement Scale (GAIS), FACE-Q module scores, and high-frequency ultrasound (USG) tissue thickness measurements at baseline and Day 120 (D120). Safety was monitored throughout. Results: The median consensus IBSA scores decreased significantly from 4.0 at baseline to 2.0 at both D30 and D120 (p-value < 0.01), indicating a rapid and sustained reduction in laxity. At D120, the GAIS responder rate reached 100% according to independent evaluators and 90.9% based on patient self-assessments. Quantitative USG confirmed statistically significant bilateral tissue thickening across the epidermis, dermis, and subcutaneous strata (p-value < 0.05). Progressive, clinically meaningful improvements were captured via the FACE-Q scales. No local or systemic adverse events were observed. Conclusions: The STIIM UP Protocol is a safe and effective multilayer intervention that successfully achieves comprehensive neck rejuvenation, bridging immediate clinical enhancement with sustained, tissue-proven structural remodeling. Full article

Post-inflammatory hyperpigmentation (PIH) results from inflammatory responses that leave persistent dark spots around pores after acne lesions are resolved. This pigmentation is caused by increased melanogenesis in melanocytes stimulated by acne-causing bacteria, followed by phagocytosis of excess melanin by macrophages that remain in the dermis. Therefore, to eliminate PIH caused by acne, it is essential not only to suppress excessive melanin synthesis by melanocytes but also to promote the degradation of melanin retained within macrophages. In this study, we investigated whether a culture extract of Bacillus velezensis AmoreLumina (AL), containing more than 80% moranoline (1-Deoxynojirimycin), could inhibit acne-induced pigmentation. Moranoline reduces melanin synthesis by inhibiting the glycosylation of tyrosinase, a key melanogenic enzyme, thereby suppressing its activity. The extract suppressed the upregulation of melanogenic enzymes (tyrosinase, TRP1, and TRP2) and melanin production in melanocytes exposed to acne bacteria, while promoting melanin degradation via macrophage lysosomal activity, as assessed by the relative protein expression level of p62 using Western blotting. Furthermore, in an ex vivo human skin model subjected to acne and ultraviolet radiation-induced pigmentation, treatment with the extract (0.2%) significantly reduced pigmentation (relative delta L 2.98, p value < 0.01). These findings suggest that cosmetic or pharmaceutical formulations incorporating AL extract or moranoline may potentially improve PIH caused by acne-related inflammation. Full article

Background: Dermal interstitial fluid (ISF) contains both plasma-derived biomarkers and biomarkers unique to ISF, making it a promising biofluid for painless, scalable, and decentralized liquid biopsy and continuous health monitoring. However, efficient ISF collection remains challenging due to the small accessible fluid volume in the dermis, slow physiological turnover, and stratum corneum. Methods: This review reframes dermal ISF sampling as a pressure gradient engineering problem using Darcy’s law. We examine how vacuum-assisted microneedle platforms can effectively drive ISF through the dermal extracellular matrix in a minimally invasive manner. We compare the two architectures: micropore-based and hollow microneedle approaches. Results: In the micropore approach, a vacuum chamber is placed over the transient micropores left by withdrawn microneedles, supporting off-device, multi-omic downstream analyses of the collected ISF. The hollow microneedle approach retains the microneedles in the skin and applies vacuum through internal lumens, allowing integration of the vacuum source, microneedles, and biosensors into a single wearable platform for in situ biomarker detection. Comparative studies across these architectures identify the vacuum seal between the device and the skin as the major engineering bottleneck shared by both architectures. Conclusions: Vacuum-assisted microneedle platforms provide a practical route for generating pressure gradient-driven ISF transport while preserving minimally invasive skin access. Future development should prioritize device–skin vacuum seal robustness, reproducible ISF recovery across users and skin sites, integrated vacuum sources, scalable fabrication, and usability in clinical or at-home settings. Full article

Collagen VI-related myopathies (COL6-RM) are rare hereditary disorders characterized by skeletal muscle dysfunction and skin manifestations, including keratosis pilaris, hypertrophic scars, and keloids. We recently found that alopecia is a novel and previously unrecognized scalp phenotype in COL6-RM; however, the precise pathogenetic mechanisms underlying hair follicle dysfunction in these patients remain incompletely understood. We performed a comprehensive immunohistochemical, ultrastructural, and proteomic characterization of scalp biopsies from six COL6-RM patients presenting with hair loss and scalp itching. We found structural alterations in the hair follicle extracellular matrix architecture, particularly in the inner fibrous sheath surrounding the hair follicle. In addition, the analysis of the perifollicular adipose tissue and derived cell cultures showed changes in lipid droplet size consistent with a tendency toward cell hypertrophy. Strikingly, proteomic profiling of adipokines revealed a pro-inflammatory and extracellular matrix-remodeling signature. Consistent with inflammation and extracellular matrix remodeling, CD68 macrophages and MMP2 expression were increased in the dermis of COL6-RM patients, particularly around the perifollicular adipocytes. Overall, these data indicate a complex pathological signature involving ECM and adipose tissue remodeling. In this context, collagen VI emerges as a potential regulator of the hair follicle microenvironment. Full article

Objectives: Microneedling is a minimally invasive procedure intended to improve skin quality through controlled mechanical stimulation of the dermis; however, objective data on its effects remain limited. This study aimed to evaluate regional changes in skin hydration and firmness after a series of microneedling treatments of the neck and décolleté using corneometry, indentometry, and patient-reported outcomes. Methods: The study included 30 female patients who underwent three microneedling sessions performed at 4-week intervals. Instrumental measurements (corneometry and indentometry) and photographic documentation were obtained before treatment initiation and 4 weeks after completion of the treatment series. Statistical analysis included linear mixed models (LMMs), Spearman’s rank correlation, and Friedman’s test for repeated measurements. Results: Microneedling produced heterogeneous responses depending on anatomical location. In corneometry analyses excluding the control point, a significant increase in hydration was observed only at point 4, while no significant changes were detected at the remaining treatment sites. Similarly, indentometry demonstrated a localized improvement in firmness exclusively at point 4, reflected by decreased indentation values after treatment. In models including the control point, no generalized time effect was observed for either corneometry or indentometry; however, significant effects of anatomical location and location-by-time interactions persisted, indicating site-dependent variability in treatment response. Age was not associated with global treatment outcomes; however, a significant age-by-location interaction was identified for indentometry. No significant correlations were found between objective instrumental measurements and subjective assessments of hydration or firmness, despite most participants reporting perceived clinical improvement. Additionally, the depth at which pinpoint bleeding occurred increased significantly across subsequent treatment sessions. Conclusions: Microneedling of the neck and décolleté resulted in localized rather than generalized instrumental skin changes, with treatment response strongly influenced by anatomical location. Objective measurements did not correlate with patient-reported improvement, highlighting the complexity of assessing esthetic treatment outcomes. However, the results should be treated cautiously due to the exploratory nature of this study. Full article

Histopathologic melanoma diagnosis extends beyond melanocytic cytology to encompass non-melanocytic features: solar elastosis patterns, stromal regression, adnexal relationships, epidermal reaction patterns, and the host inflammatory response. These “old school” low-power clues are particularly valuable on sun-damaged skin, where benign nevi, reactive melanocytic hyperplasia, and melanoma in situ share overlapping features. Quantitative data support two elastosis-based signs: the “umbrella sign” (reduced elastosis beneath the lesion’s central third; PPV (Positive Predictive Value) for nevus, 96%, and NPV (Negative predictive Value) for melanoma, 74%; calculated from raw cohort data) and the “purple fiber sign” (100% specificity, 30% sensitivity for nevus), both from a cohort of 81 actinically damaged lesions. Regression—identified by compressed elastic layers displaced to the reticular dermis, fibrosis, melanophages, and inflammation—aids diagnosis but complicates distinction from surgical scar. The maturation state of tertiary lymphoid structures (TLSs) within the regression zone, ranging from immunosuppressive immature aggregates to anti-tumoral mature structures with germinal centers, may explain the variable prognostic significance of histologic regression. Epidermal hyperplasia over thick melanomas reflects angiogenesis-related changes, while effacement is a practical red flag in spitzoid lesions. Ancillary tests are most productive when morphology has already framed the differential. These non-melanocytic clues remain indispensable as the foundation for rational ancillary testing. Full article

Introduction. Psoriasis is a chronic inflammatory disease histologically characterized by epidermal hyperproliferation, altered keratinocyte differentiation and dermal vascular remodeling. Although the diagnosis is mainly clinical, non-invasive imaging methods, such as high-frequency skin ultrasound, allow an objective assessment of skin changes and disease activity. Material and Methods. We conducted a pilot, observational, cross-sectional and comparative study, conducted within the Dermatovenerology Department of the Central Military Emergency Hospital “Dr. Carol Davila”, Bucharest, which included 40 patients diagnosed with psoriasis vulgaris, of whom 22 received conventional systemic treatment (methotrexate 15 mg/week), and 18 received biological therapy. For each patient, a representative, clinically active and recently appeared psoriatic plaque was evaluated with ultrasound, and the thickness of the epidermis, the thickness of the dermis, the thickness of the hypoechoic subepidermal band (SLEB) and the Doppler signal were analyzed. Statistical analysis was performed using SPSS v26. Results. Patients under biologic therapy had significantly lower ultrasound parameters compared to those under conventional systemic therapy, especially regarding epidermis thickness, hypoechoic subepidermal band thickness and Doppler signal. The PASI score was significantly higher in the conventionally treated group. Also, significant positive correlations were found between the PASI score and the hypoechoic subepidermal band thickness and the Doppler signal, Conclusions. Ultrasound parameters represent useful objective markers in the evaluation of psoriasis, reflecting disease activity. Patients under biologic therapy presented, at the time of evaluation, imaging parameters suggestive of reduced skin inflammation compared to those treated conventionally. Full article

The integument of elasmobranchs is a complex biomechanical system in which epithelial, connective tissue and mineralised components form a functionally specialised body surface. Despite extensive research on dermal denticles, the spatial configuration of the whole integument, especially the regional arrangement of collagen fibres in benthic species, remains poorly understood. This study provides an integrated characterisation of the skin microarchitecture of the Arabian carpetshark (Chiloscyllium arabicum), with emphasis on regional variability in dermal denticles and collagen matrix structuring. Skin samples were analysed using haematoxylin and eosin, Masson–Goldner, PAS–Alcian blue and picrosirius red staining, together with transmitted and polarised light microscopy and morphometric analysis. The skin of this species showed a hierarchical organisation comprising a stratified epithelium and a complex fibrous dermis. Dermal denticles displayed typical elasmobranch anatomy, but their morphology, orientation, and density varied regionally, allowing five morphotypes to be distinguished. Collagen fibres formed ordered, plywood-like and orthogonal arrangements showing spatial correspondence with local denticle distribution. These findings indicate regional structural specialisation of the integument and suggest a structural association, and a possible functional relationship, between denticle morphology and collagen architecture. Full article

Skin aging reflects the accumulation of molecular damage and a progressive disruption of dermal mechanical homeostasis. Fragmentation and disorganization of the dermal extracellular matrix (ECM) impair force transmission to resident fibroblasts. Reduced cell spreading and mechanical force generation are associated with increased matrix metalloproteinase expression and reduced collagen synthesis, partly through c-Jun/AP-1 activation and attenuation of TGF-β/TβRII signaling. Reduced YAP/TAZ mechanosignaling has also been linked to cGAS-STING-dependent senescence in experimental models. However, its causal role in aging human dermis remains unresolved. This narrative review considers dermal mechanobiology as an integrative framework alongside ultraviolet exposure, oxidative stress, glycation, and cellular senescence. It examines how injectable fillers may influence the dermal mechanical microenvironment. A filler’s material properties may constitute a mechanical exposure, although bulk rheological measurements do not define force transmission at the cellular scale. Human in vivo studies of cross-linked hyaluronic acid provide the most direct evidence that enhanced structural support is associated with fibroblast spreading, activation of TGF-β-related signaling, and increased type I collagen deposition. Evidence for calcium hydroxylapatite and other biostimulatory fillers is complementary but more heterogeneous. A composite of PEGDE-cross-linked hyaluronic acid and calcium hydroxylapatite microspheres is considered as an explicitly preliminary example. This review defines the current evidence, its key limitations, and the mechanistically informed studies needed to determine whether, and which, fillers can meaningfully modify dermal mechanobiology. Full article

Syphilis remains one of the most prevalent sexually transmitted infections. Serology is the diagnostic gold standard, but skin biopsies aid in ambiguous cases. Treponemas can be detected in tissue by immunohistochemistry (IHC) and polymerase chain reaction (PCR); however, their comparative performance across disease stages has not been extensively studied. This retrospective study of 48 formalin-fixed, paraffin-embedded (FFPE) skin biopsies from syphilis cases compared Treponema pallidum IHC and PCR. Of 48 biopsies, 42 (88%) were positive by T. pallidum–specific PCR, whereas IHC identified 45 (94%; p = 0.04). Organisms were denser in primary syphilis (p = 0.03) and predominantly involved the lower third of the epidermis. In 7 of 45 biopsies (15%), treponemas were only detected in the dermis (all secondary syphilis). Therefore, Treponema pallidum IHC demonstrated a slight advantage over PCR, but low Treponema density in about 40% and epidermal absence in nearly 20% of secondary syphilis biopsies highlight a substantial risk of overlooking treponemas on IHC. Systematic assessment including endothelium and perivascular areas is essential. Full article