Search Results (208)

Medical phantoms are essential to imaging calibration, clinician training, and the validation of therapeutic procedures. However, most ultrasound phantoms prioritize acoustic realism while neglecting the viscoelastic and anisotropic properties of fibrous soft tissues. This gap limits their effectiveness in modeling realistic biomechanical behavior, especially in wave-based diagnostics and therapeutic ultrasound. Current materials like gelatine and agarose fall short in reproducing the complex interplay between the solid and fluid components found in biological tissues. To address this, we developed a soft, anisotropic composite whose dynamic mechanical properties resemble fibrous biological tissues such as skin and skeletal muscle. This material enables wave propagation and vibration studies in controllably anisotropic media, which are rare and highly valuable. We demonstrate the tunability of damping and stiffness aligned with fiber orientation, providing a versatile platform for modeling soft-tissue dynamics and validating biomechanical simulations. The phantoms achieved Young’s moduli of 7.16–11.04 MPa for skin and 0.494–1.743 MPa for muscles, shear wave speeds of 1.51–5.93 m/s, longitudinal wave speeds of 1086–1127 m/s, and sound absorption coefficients of 0.13–0.76 dB/cm/MHz, with storage, loss, and complex moduli reaching 1.035–6.652 kPa, 0.1831–0.8546 kPa, and 2.138–10.82 kPa. These values reveal anisotropic response patterns analogous to native tissues. This novel natural fibrous composite system affords sustainable, low-cost ultrasound phantoms that support both mechanical fidelity and acoustic realism. Our approach offers a route to next-gen tissue-mimicking phantoms for elastography, wave propagation studies, and dynamic calibration across diverse clinical and research applications. Full article

During the service life of automotive panel stamping dies, the surface is often subjected to high loads and repeated friction, resulting in excessive wear. This leads to die failure, reduced machining accuracy, and decreased production efficiency. To enhance the anti-friction and wear-resistant performance of die steel surfaces, this study introduces the concept of biomimetic engineering in surface science. By mimicking microstructural configurations found in nature with outstanding wear resistance, biomimetic functional surfaces were designed and fabricated. Specifically, quadrilateral dimples inspired by the back of dung beetles, pentagonal scales from armadillo skin, and hexagonal scales from the belly of desert vipers were selected as biological prototypes. These surface textures were fabricated on Cr12MoV die steel using high-speed ball-end milling. Finite element simulations and dry sliding wear tests were conducted to systematically investigate the tribological behavior of surfaces with different dimple geometries. The results showed that the quadrilateral dimple surface derived from the dung beetle exhibited the best performance in reducing friction and wear. Furthermore, the milling parameters for this surface were optimized using response surface methodology. After optimization, the friction coefficient was reduced by 21.3%, and the wear volume decreased by 38.6% compared to a smooth surface. This study confirms the feasibility of fabricating biomimetic functional surfaces via high-speed ball-end milling and establishes an integrated surface engineering approach combining biomimetic design, efficient manufacturing, and parameter optimization. The results provide both theoretical and methodological support for improving the service life and surface performance of large automotive panel dies. Full article

Transdermal microneedle systems have received great attention due to their minimally invasive way of delivering biomolecules through the skin with reduced pain. However, designing high-strength separable microneedles, which enable easy skin penetration and easy patch detachment, is challenging. Here, we present a Parametric Rule-based Intelligent System (PRISM), which generates the design of and analyzes high-strength separable microneedles. The PRISM platform integrates parametric 3D modeling, geometry-based structural analysis, and high-resolution micro-3D printing for the creation of high-strength separable microneedles. We fabricated prototype microneedle arrays via microscale stereolithographic printing (pµSL) and demonstrated separation of microneedle tips in a skin-mimicking phantom sample. Mechanical testing showed that the suggested design achieved 2.13 ± 0.51 N axial resistance and 73.92 ± 34.77 mN shear fracture force; this surpasses that of conventional designs. Finally, an experiment using a skin-mimicking artificial phantom sample confirmed that only the PRISM-designed separable microneedles could have been inserted and separated at the target depth, whereas conventional designs failed to detach. This approach addresses the development of microneedle systems, which achieve both robust skin phantom penetration and reliable separable delivery, presenting an efficient development tool in transdermal drug delivery technology. Full article

Background/Objectives: Melanoma is one of the most aggressive forms of skin cancer and is frequently associated with the B-Raf⁶⁰⁰E mutation, which constitutively activates the MAPK signaling pathway. Although selective inhibitors such as Vemurafenib offer clinical benefits, their long-term efficacy is often hindered by resistance mechanisms and adverse effects. In this study, twelve phytochemicals from Brazilian green propolis were evaluated for their potential as selective B-Raf⁶⁰⁰E inhibitors using a computational approach. Methods: Physicochemical, ADME, and electronic properties were assessed, followed by molecular docking using the B-Raf⁶⁰⁰E crystal structure (PDB ID: 3OG7). Redocking validation and 500 ns molecular dynamics simulations were performed to investigate the stability of the ligand-protein complexes, and free energy calculations were then computed. Results: Among the tested compounds, Artepillin C exhibited the strongest binding affinity (−8.17 kcal/mol) in docking and maintained stable interactions with key catalytic residues throughout the simulation, also presenting free energy of binding ΔG of −20.77 kcal/mol. HOMO-LUMO and electrostatic potential analyses further supported its reactivity and selectivity. Notably, Artepillin C remained bound within the ATP-binding site, mimicking several critical interactions observed with Vemurafenib. Results: Among the tested compounds, Artepillin C exhibited the strongest binding affinity (−8.17 kcal/mol) and maintained stable interactions with key catalytic residues throughout the simulation. HOMO-LUMO and electrostatic potential analyses further supported its reactivity and selectivity. Notably, Artepillin C remained bound within the ATP-binding site, mimicking several critical interactions observed with Vemurafenib. Conclusions: These findings indicate that Artepillin C is a promising natural compound for further development as a selective B-Raf⁶⁰⁰E inhibitor and suggest its potential utility in melanoma treatment strategies. This study reinforces the value of natural products as scaffolds for targeted drug design and supports continued experimental validation. Full article

Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. Methods: We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome–immune interactions, including data from ongoing nutritional clinical trials. Results: Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. Conclusions: Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor–immune–microbiome axis. When combined with AI-driven nutrient–protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies. Full article

Background: Pulmonary fibrosis is a major disease that leads to the progressive loss of lung function. The disease manifests early, resulting in type 2 respiratory failure. This is likely due to the bronchocentric fibrosis around the major airways, which causes airflow limitation. It affects approximately three million patients worldwide and has a poor prognosis. Skin fibroblasts isolated from patients offer valuable insights into understanding the disease mechanisms, identifying the genetic causes, and developing personalized therapies. However, the use of skin fibroblasts to study a disease that exclusively impacts the lungs is often questioned, particularly since lung fibrosis primarily affects the alveolar epithelium. Method: We report the reprogramming of skin fibroblasts from patients with an atypical early-onset form of lung fibrosis into induced pluripotent stem cells (iPSCs) and subsequently into alveolar epithelial cells. This was achieved using a Sendai virus approach. Results: We show that the reprogrammed cells carry mutations in the calcium-binding protein genes S100A3 and S100A13, leading to diminished protein expression, thus mimicking the patients’ cells. Additionally, we demonstrate that the generated patient iPSCs exhibit aberrant calcium and mitochondrial functions. Conclusions: Due to the lack of a suitable animal model that accurately resembles the human disease, generating patient lung cells from these iPSCs can provide a valuable “disease in a dish” model for studying the atypical form of inherited lung fibrosis. This condition is associated with mutations in the calcium-binding protein genes S100A3 (NM_002960) and S100A13 (NM_001024210), aiding in the understanding of its pathogenesis. Full article

Non-tuberculous mycobacteria (NTM) are saprophytes of both soil and water that may cause infection with a high risk of dissemination, mainly in immunocompromised patients. Most NTM infections occur in the lungs, while uncommon localizations are the skin, soft tissues, musculoskeletal apparatus, and lymphatic system. The possible relationship between NTM infections and dental procedures is still unclear. The authors reported a rare manifestation of NTM infection occurring in a 6-year-old girl who developed sub-mandibular swelling related to a necrotic tooth, thus mimicking an abscess of odontogenic origin. Fine-needle aspiration biopsy of the sub-mandibular swelling and the following microbiologic investigation showed infection sustained by the Mycobacterium fortuitum complex. After the medical and surgical treatment, the patient completely recovered after 8 months. A review of the relevant literature was carried out to deepen the clinical and microbiological aspects of such a rare occurrence. Full article

(1) Background: The increasing prevalence of chronic wounds, along with their significant healthcare burden, underscores the need for innovative and technologically advanced treatment strategies. Electrospun nanofiber-based dressings have emerged as a promising solution, mimicking the skin’s extracellular matrix and promoting efficient tissue regeneration. (2) Methods: This real-world, 10-month observational study conducted at CF Oradea Clinical Hospital enrolled 60 patients with chronic, non-healing wounds. Patients were randomly assigned to two groups: 30 received standard vacuum-assisted wound therapy, serving as the control group. In contrast, 30 received treatment with Spincare™, a novel electrospinning technology that delivers a personalized nanofiber matrix directly onto the wound. Symptom progression, pain levels, and treatment adaptation were assessed using standardized questionnaires. (3) Results: Patients treated with Spincare™ demonstrated faster wound healing, especially in the epithelialization phase, with significantly improved pain scores and quality of life measures. The technology was well-tolerated and reduced the need for repeated hospitalizations. (4) Conclusions: Spincare™ represents an effective and innovative electrospun nanofiber solution for chronic wound management, accelerating healing and enhancing patient outcomes, particularly in individuals with underlying conditions such as peripheral arterial disease. These findings support the integration of electrospinning-based therapies in modern wound care protocols. Full article

Non-invasive glucose monitoring has become a critical area of research for diabetes management, offering a less intrusive and more patient-friendly alternative to traditional methods such as finger-prick tests. This study presents a novel approach using a semi-solid tissue-mimicking phantom designed to replicate the dielectric properties of human skin and blood vessels. The phantom was simplified to focus solely on the skin layer, with embedded channels representing veins to achieve realistic glucose monitoring conditions. These channels were filled with D-(+)-Glucose solutions at varying concentrations (60 mg/dL to 200 mg/dL) to simulate physiological changes in blood glucose levels. A miniature patch antenna optimized to operate at 14 GHz with a penetration depth of approximately 1.5 mm was designed and fabricated. The antenna was tested in direct contact with the skin phantom, allowing for precise measurements of the changes in glucose concentration without interference from deeper tissue layers. Simulations and experiments demonstrated the antenna’s sensitivity to variations in glucose concentration, as evidenced by measurable shifts in the dielectric properties of the phantom. Importantly, the system enabled stationary measurements by injecting glucose solutions into the same blood vessels, eliminating the need to reposition the sensor while ensuring reliable and repeatable results. This work highlights the importance of shallow penetration depth in targeting close vessels for noninvasive glucose monitoring, and emphasizes the potential of microwave-based sensing systems as a practical solution for continuous glucose management. Full article

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article

Background: Fabry disease (FD) results from pathogenic GLA variants, causing lysosomal α-galactosidase A (α-GalA) deficiency and sphingolipid ceramide trihexoside (Gb3 or THC) accumulation. Disease phenotype varies widely but cardiomyopathy is commonly life-limiting. As a multisystemic disorder, FD initiates at the cellular level; however, the mechanism/s underlying Gb3-induced cell dysfunction remains largely unknown. This study established an in vitro mutation-specific model of Fabry cardiomyopathy using human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes to explore underlying cell pathology. Methods: Skin biopsies from consenting Fabry patients and normal control subjects were reprogrammed to iPSCs then differentiated into cardiomyocytes. The GLA mutations in Fabry cell lines were corrected using CRISP-Cas9. Phenotypic characteristics, α-Gal A activity, Gb3 accumulation, functional status, and lipid analysis were assessed. Cardiomyocytes derived from two patients with severe clinical phenotype and genotypes, GLA^c.851T>C, GLA^{c.1193_1196del}, and their respective corrected lines, GLA^{corr c.851T>C}, GLA^{corr c.1193_1196del}, were selected for further studies. Results: Cardiomyocytes derived from individuals with FD iPSCs exhibited stable expression of cardiomyocyte markers and spontaneous contraction, morphological features of FD, reduced α-Gal A activity, and accumulation of Gb3. Lipidomic profiling revealed differences in the Gb3 isoform profile between the control and FD patient iPSC-derived cardiomyocytes. Contraction strength was unchanged but relaxation after contraction was delayed, mimicking the diastolic dysfunction typical of Fabry cardiomyopathy. Conclusions: iPSC-derived cardiomyocytes provide a useful model to explore aspects of Fabry cardiomyopathy, including disruptions in sphingolipid pathways, proteomics, and multigene expression that together link genotype to phenotype. The platform potentially offers broad applicability across many genetic diseases and offers the prospect of testing and implementation of individualised therapies. Full article

Aging, marked by a decline in cellular function and increased risk of diseases, involves the accumulation of senescent cells. This study aims to develop and characterize 3D senescent skin models to understand cellular senescence mechanisms’ implications in cutaneous aging. Normal human epidermal keratinocytes (NHEKs) were cultured from early to late passages (p2 to p7) to induce replicative senescence or sourced from both young and aged donors to reconstruct 3D models. Histological analyses assessed tissue morphology and integrity, while permeability assays evaluated epidermal barrier function. Analyses using immunostaining, RT-PCR, Affymetrix™ GeneChip™ Microarrays identified key markers of cellular senescence, epidermal homeostasis, and other related processes. Results showed that NHEKs at p5 and beyond, and those from aged donors, exhibited significant morphological disruptions, decreased expression of differentiation-associated genes, and impaired barrier function. Increased p16ink4a-positive cells indicated enhanced senescence. Transcriptome analysis revealed significant changes in keratinocyte differentiation, cell–cell interaction, cell cycle regulation, extracellular matrix homeostasis, and inflammation. These findings underscore the relevance of addressing cellular senescence for enhancing skin health and promoting skin longevity. These 3D senescent skin models, validated by consistent results from both passage-induced senescence and aged donor keratinocytes, are valuable for understanding skin aging and developing anti-aging treatments, positioning them as essential tools in the pursuit of skin longevity-focused innovations. Full article

Psoriasis is a chronic immune-mediated skin disease characterized by cytokine dysregulation. Pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17, and IL-23, play pivotal roles in the pathogenesis of psoriasis. Emerging evidence suggests that dietary interventions can modulate cytokine activity, providing a complementary approach to standard therapies. This narrative review examines the impact of various dietary strategies, including a Mediterranean diet, ketogenic diet, gluten-free diet, and fasting-mimicking diet, on cytokine profiles and clinical outcomes in psoriasis. Research insights reveal that dietary components such as omega-3 fatty acids, polyphenols, and short-chain fatty acids influence immune signaling pathways. These pathways include nuclear factor-kappa B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3). Additionally, these dietary components promote anti-inflammatory effects mediated by gut microbiota. Clinical studies demonstrate significant reductions in psoriasis severity, improved quality of life, and modulation of key cytokines associated with disease activity. Despite these advancements, significant challenges persist in effectively integrating these findings into clinical practice. These challenges include variability in patient responses, adherence issues, and the need for robust biomarkers to monitor efficacy. Future directions emphasize the potential of personalized nutrition and precision medicine approaches to optimize dietary interventions tailored to individual cytokine profiles and genetic predispositions. Integrating these strategies into psoriasis care could transform treatment paradigms by simultaneously addressing both systemic inflammation and comorbid conditions. Full article

Over 100 years after its commercialization, the insulin administration method still needs elementary education. Such observation contrasts with technological progress constantly elaborating new (e.g., weekly) insulin preparations, capable of mimicking the pharmacokinetics of insulin produced by the human pancreas and exploring alternatives to injection. However, insulin administration remains anchored to the subcutaneous route, thus creating the conditions for lipohypertrophies (LHs), a still too frequent and ubiquitously widespread skin complication that, despite being avoidable with an adequate educational path, affects up to 60% of patients and even more. Considering that there are approximately 580 million adult diabetic people in the world today, at least half of whom (290 million) self-inject insulin, should 50% of the latter have LH, approximately 145 million people and even more? Considering that there are approximately 580 million adult diabetic people in the world today, at least half of whom (290 million) self-inject insulin, should 50% of the latter have LH, approximately 145 million people would suffer from such a complication, thus causing a severe problem for the global health system. Indeed, besides being unsightly, LHs cause poor glycemic control, large glucose variability, and frequent unexplained hypoglycemia, and display a strong correlation with micro- and macrovascular complications, inevitably worsening the quality of life of diabetic people. In this narrative review, after a brief description of the alternative routes of administration to subcutaneous injections, we will recall the causes, consequences, and possible corrective actions of LHs, stigmatizing the fundamental role of therapeutic education and hoping that all this can interest all the actors who revolve around the management of insulin therapy, which is too often underestimated and hastily addressed by health professionals, who probably prefer to dedicate time to titration of therapy. Ultimately, our aim is to provide the reader with a practical review of injection errors resulting from incorrect insulin injection techniques, analyzing the leading causes of error and the consequences of these errors, while also providing advice and suggestions to overcome all this. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, immune dysregulation, and vascular dysfunction, yet its pathogenesis remains incompletely understood. This study compares two widely used animal models of SSc—the bleomycin-induced fibrosis model and the collagen-V-induced autoimmune model—to evaluate their ability to replicate key disease features. In the bleomycin model, consistent cardiac fibrosis was observed across treatment groups despite variability in fibrosis in the skin and lungs, suggesting organ-specific differences in susceptibility. The collagen-V model demonstrated robust autoantibody production against collagen-V, confirming its utility in studying immune activation, though fibrosis was largely confined to the heart. While the bleomycin model excels at mimicking rapid fibrosis and is suitable for testing antifibrotic therapies, the collagen-V model provides insights into antigen-specific autoimmunity. Both models highlight the dynamic nature of fibrosis, where ECM deposition and degradation occur concurrently, complicating its use as a quantitative disease marker. Cardiac fibrosis emerged as a consistent feature in both models, emphasizing its relevance in SSc pathophysiology. Combining these models or refining their design through hybrid approaches, extended timelines, or sex and age adjustments could enhance their translational utility. These findings advance understanding of SSc mechanisms and inform therapeutic development for this challenging disease. Full article