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Liposomal drug delivery systems are successfully used in various fields of medicine for external and systemic applications. Marine organisms contain biologically active substances that have a unique structure and exhibit a wide range of biological activities. Polysaccharide of red seaweed (carrageenan (CRG)), and water-insoluble sea urchin pigment (echinochrome (Ech)) interact with each other and form a stable complex. We included the CRG/Ech complex in liposomes for better permeability into cells. In our research, tetramethylrhodamine isothiocyanate TRITC-labeled CRG was synthesized to study the interaction of the complex encapsulated in liposomes with human epidermal keratinocytes (HaCaTs) widely used to expose the skin to a variety of substances. Using confocal microscopy, we found that liposomes were able to penetrate HaCaT cells with maximum efficiency within 24 h, and pre-incubation of keratinocytes with liposomes resulted in the delivery of the CRG/Ech complex into the cytoplasm. We investigated the anti-inflammatory effects of liposomes, including the lysosomal regulation, increased intracellular ROS levels, and increased NO synthesis in lipopolysaccharide (LPS)- or Escherichia coli (E. coli)-induced inflamed skin cells. Liposomes containing the CRG/Ech complex significantly reduced lysosomal activity by 26% in LPS-treated keratinocytes and decreased ROS levels in cells by 23% after LPS exposure. It was found that liposomes with the complex improved the migration of HaCaT keratinocytes incubated with high-dose LPS by 47%. The results of the work, taking into account the good permeability of liposomes into keratinocytes, as well as the anti-inflammatory effect on cells treated with LPS or E. coli, show the prospects of using liposomes containing the CRG/Ech complex as an anti-inflammatory agent in the fight against skin infections. Full article

The development of artificial skin that accurately mimics the mechanical properties of human skin is crucial for a wide range of applications, including surgical training for burn injuries, biomechanical testing, and research in sports injuries and ballistics. While traditional materials like gelatin, polydimethylsiloxane (PDMS), and animal skins (such as porcine and bovine skins) have been used for these purposes, they have inherent limitations in replicating the intricate properties of human skin. In this work, we conducted uniaxial tensile tests on freshly obtained cadaveric skin to analyze its mechanical properties under various loading conditions. The stress–strain data obtained from these tests were then replicated using advanced skin simulants. These skin simulants were specifically formulated using a cost-effective and moldable multi-part silicone-based polymer. This material was chosen for its ability to accurately replicate the mechanical behavior of human skin while also addressing ethical considerations and biosafety concerns. In addition, the non-linear mechanical behavior of the developed skin simulants was characterized using three different hyperelastic curve-fit models (i.e., Neo-Hookean, Mooney–Rivlin, and Yeoh models). Moreover, these innovative simulants offer an ethical and practical alternative to cadaveric skin for use in laboratory and clinical settings. Full article

Cutaneous squamous cell carcinoma (CSCC) in dogs is a locally invasive tumor that typically occurs in areas of poorly pigmented skin due to sun exposure. Identifying new biomarkers, such as syndecan-1 (CD138) and E-cadherin, is fundamental for tumor diagnosis and prognosis. Dysregulation of syndecan-1, expressed in epithelial tissue, fibroblasts, and plasma cells, is associated with poor prognosis in several types of cancer. Similarly, E-cadherin, which plays a crucial role in cell adhesion and epithelial functionality, is also linked to adverse outcomes. This study evaluated the expression of syndecan-1 and E-cadherin in 47 cases of canine cutaneous squamous cell carcinoma. The results showed that the intensity of syndecan-1 decreased with increasing tumor aggressiveness, and its presence in the stroma was significantly associated with tumor grade. E-cadherin also demonstrated a decrease in intensity with increasing malignancy. However, the association between syndecan-1 and E-cadherin was not statistically significant. E-cadherin reduction and stromal syndecan-1 positivity seem to be associated with tumor aggressiveness in canine cutaneous squamous cell carcinoma. Further studies are needed to explore their roles in tumor progression. Full article

With technological advancements, remarkable progress has been made with the convergence of health sciences and Artificial Intelligence (AI). Modern health systems are proposed to ease patient diagnostics. However, the challenge is to provide AI-based precautions to patients and doctors for more accurate risk assessment. The proposed healthcare system aims to integrate patients, doctors, laboratories, pharmacies, and administrative personnel use cases and their primary functions onto a single platform. The proposed framework can also process microscopic images, CT scans, X-rays, and MRI to classify malignancy and give doctors a set of AI precautions for patient risk assessment. The proposed framework incorporates various DCNN models for identifying different forms of tumors and fractures in the human body i.e., brain, bones, lungs, kidneys, and skin, and generating precautions with the help of the Fined-Tuned Large Language Model (LLM) i.e., Generative Pretrained Transformer 4 (GPT-4). With enough training data, DCNN can learn highly representative, data-driven, hierarchical image features. The GPT-4 model is selected for generating precautions due to its explanation, reasoning, memory, and accuracy on prior medical assessments and research studies. Classification models are evaluated by classification report (i.e., Recall, Precision, F1 Score, Support, Accuracy, and Macro and Weighted Average) and confusion matrix and have shown robust performance compared to the conventional schemes. Full article

Genitourinary syndrome of menopause (GSM) affects a significant percentage of postmenopausal women and manifests as vaginal dryness, irritation, and urinary discomfort, typically treated with vaginal estrogens. Hydrogels are preferred over creams due to their superior comfort and mucoadhesive properties. This study introduces a novel vaginal gel formulation containing hydroxyethyl cellulose (HEC) and estriol-hydroxypropyl-β-cyclodextrin complex (E3-HPBCD) for the treatment of GSM. The estriol (E3) release profile of the gel was evaluated using a Franz diffusion cell system, and its permeability was tested on reconstructed human vaginal epithelium. Biocompatibility was assessed using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) assays, and real-time cell analysis (RTCA) on human skin keratinocyte (HaCaT) cells, which showed increased cell viability and no obvious cytotoxicity. The results indicated that efficient E3 release and satisfactory epithelial permeability with HPBCD provide the bioavailability of E3. These results suggest the potential of the gel as a biocompatible and effective alternative for the treatment of GSM. Further studies are required to assess the long-term safety and clinical efficacy. Full article

Background and objectives: Slit1 is a secreted protein that is closely related to cell movement and adhesion. Few studies related to fibrosis exist, and the preponderance of current research is confined to the proliferation and differentiation of neural systems. Hypertrophic scars (HTSs) are delineated by an overproduction of the extracellular matrix (ECM) by activated fibroblasts, leading to anomalous fibrosis, which is a severe sequela of burns. However, the functionality of Slit1 in HTS formation remains unknown. We aimed to investigate whether Slit1 regulates fibroblasts through a fibrosis-related mechanism derived from post-burn HTS tissues and normal patient tissues. Methods: Human normal fibroblasts (HNFs) and hypertrophic scar fibroblasts (HTSFs) were extracted from normal skin and post-burn HTS tissues, with settings grouped according to the patient of origin. Cell proliferation was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay Kit. Cell migration experiments were carried out using a μ-Dish insert system. Protein and mRNA expression levels were quantified by Western blot and quantitative real-time polymerase chain reaction. Results: We found increased expressions of Slit1 in HTS tissues and HTSFs compared to normal tissues and HNFs. The treatment of human recombinant Slit1 protein (rSlit1) within HNFs promoted cell proliferation and differentiation, leading to an upregulation in ECM components such as α-SMA, type I and III collagen, and fibronectin. The treatment of rSlit1 in HNFs facilitated cell migration, concurrent with enhanced levels of N-cadherin and vimentin, and a diminished expression of E-cadherin. Treatment with rSlit1 resulted in the phosphorylation of SMAD pathway proteins, including SMAD2, SMAD3, and SMAD1/5/8, and non-SMAD pathway proteins, including TAK1, JNK1, ERK1/2, and p38, in HNFs. Conclusions: Exogenous Slit1 potentiates the epithelial–mesenchymal transition and upregulates SMAD and non-SMAD signaling pathways in HNFs, leading to the development of HTS, suggesting that Slit1 is a promising new target for the treatment of post-burn HTS. Full article

Dullness or lack of radiance in facial appearance is a common concern among females. Previous studies have linked skin dullness to aging and revealed alterations in skin pigments. However, younger individuals (ages ≤ 35) also report concerns about dull skin in their hectic daily lives, which may not involve pigmentation changes. We hypothesized that the mechanisms underlying dullness in youth differ from those associated with aging. To investigate this, we measured cellular and molecular changes in 132 healthy Japanese and Chinese females aged 18 to 35 using biophotonic multiphoton tomography and biochemical tape-strip analysis. Our findings revealed that dull skin exhibited a thicker stratum granulosum and less densely packed keratinocytes in deeper layers. Biochemical analysis showed upregulation of interleukin-36γ and downregulation of E-cadherin in dull skin, with interleukin-36γ levels negatively correlating (p = 0.023) with metabolites of filaggrin. These alterations resemble those observed in inflammatory skin conditions, suggesting an additional mechanism of skin dullness beyond pigmentation. In vitro cultured cell models evaluated the efficacy of three skincare ingredients: galactomyces fermentation filtrate, bisabolol, and batyl alcohol. Galactomyces suppressed interleukin-36γ (p = 0.037), while both batyl alcohol (p = 0.006) and bisabolol (p = 0.049) showed beneficial effects on filaggrin. Targeting these biomarkers may improve the appearance of dull skin. Full article

Among the physical decontamination methods, treatment with ultraviolet (UV) radiation is a suitable means of preventing viral infections. Mercury vapor lamps (254 nm) used for room decontamination are potentially damaging to human skin (radiation) and harmful to the environment (mercury). Therefore, other UV-C wavelengths (100–280 nm) may be effective for virus inactivation on skin without damaging it, e.g., far-UV-C radiation with a wavelength of 233 nm, which is absorbed in the outer layer of the skin and thus does not reach the deeper layers of the skin. For room disinfection, 275 nm UV-C LED lamps could be a more environmentally friendly alternative, since toxic mercury is avoided. A carrier test using multiple viruses was used to determine the TCID₅₀/mL value on stainless steel, PVC, and glass carriers. In addition to the inactivation kinetics (233 nm), the necessary UV-C dose for 4 lg inactivation (275 nm) was investigated. The impact of irradiance on the inactivation efficacy was also assessed. The inactivation of the viruses was a function of the radiation dose. UV-C-radiation at 233 nm (80 mJ/cm²) inactivated from 1.49 ± 0.08 to 4.28 ± 0.18 lg depending on the virus used. To achieve a 4 lg inactivation (275 nm) for enveloped viruses, doses of up to 70 mJ/cm² (SuHV-1) were sufficient. For non-enveloped viruses, a maximum dose of 600 mJ/cm² (MS2) was necessary. Enveloped viruses were inactivated with lower doses compared to non-enveloped viruses. Higher radiation doses were required for inactivation at 275 nm in comparison to 254 nm. A more environmentally friendly alternative to mercury vapor lamps is available with 275 nm LED emitters. Radiation at 233 nm could serve as an additional prophylactic or therapeutic measure for virus inactivation in direct contact with human skin. Full article

Bovine milk is widely recognized as one of the most valuable sources of nutrients such as proteins, fats, vitamins, and minerals that support the development and health of the body. In recent years, there has been increasing scientific interest in exosomes, the small membrane-bound vesicles found in milk. Through their content (e.g., microRNA), exosomes can influence gene expression and modulate key signaling pathways within target cells. Results from in vitro and in vivo studies have shown that bovine milk-derived exosomes can alleviate intestinal inflammation by regulating signaling pathways and positively influencing the composition of the gut microbiota. They also improve cognitive function and support nervous system regeneration. In addition, exosomes promote bone health by stimulating osteoblast formation and inhibiting bone resorption, helping to prevent osteoporosis. Studies have shown that exosomes have beneficial effects on skin health by promoting collagen production, protecting cells from oxidative stress, and delaying the ageing process. Bovine milk-derived exosomes are a promising tool for the treatment and prevention of a variety of diseases, particularly those related to inflammation and tissue regeneration. Although these results are promising, further studies are needed to fully understand the mechanisms of action and the potential clinical application of milk exosomes in the prevention and treatment of different diseases. Full article

Traumatic brain injury (TBI) during snowboarding sports is a major concern. A robust evaluation of existing snowboarding helmets is desired. Head kinematics (i.e., linear acceleration, angular velocity, angular acceleration) and associated brain responses (brain pressure, equivalent (von Mises) stress, and maximum principal strain) of the head are a predominant cause of TBI or concussion. The conventional snowboarding helmet, which mitigates linear acceleration, is typically used in snow sports. However, the role of conventional snowboarding helmets in mitigating angular head kinematics is marginal or insignificant. In recent years, new anti-rotational technologies (e.g., MIPS, WaveCel) have been developed that seek to reduce angular kinematics (i.e., angular velocity, angular acceleration). However, investigations regarding the performance of snowboarding helmets in terms of the mitigation of head kinematics and brain responses are either extremely limited or not available. Toward this end, we have evaluated the performance of snowboarding helmets (conventional and anti-rotational technologies) against blunt impact. We also evaluated the performance of newly developed low-cost, silica-based anti-rotational pads by integrating them with conventional helmets. Helmets were mounted on a head surrogate–Hybrid III neck assembly. The head surrogate consisted of skin, skull, dura mater, and brain. The geometry of the head surrogate was based on the GHBMC head model. Substructures of the head surrogate was manufactured using additive manufacturing and/or molding. A linear impactor system was used to simulate/recreate snowfield hazards (e.g., tree stump, rock, pole) loading. Following the ASTM F2040 standard, an impact velocity of 4.6 ± 0.2 m/s was used. The head kinematics (i.e., linear acceleration, angular velocity, angular acceleration) and brain simulant pressures were measured in the head surrogate. Further, using the concurrent simulation, the brain simulant responses (i.e., pressure, von Mises stress, and maximum principal strain) were computed. The front and side orientations were considered. Our results showed that the helmets with anti-rotation technologies (i.e., MIPS, WaveCel) significantly reduced the angular kinematics and brain responses compared to the conventional helmet. Further, the performance of the silica pad-based anti-rotational helmet was comparable to the existing anti-rotational helmets. Lastly, the effect of a comfort liner on head kinematics was also investigated. The comfort liner further improved the performance of anti-rotational helmets. Overall, these results provide important data and novel insights regarding the performance of various snowboarding helmets. These data have utility in the design and development of futuristic snowboarding helmets and safety protocols. Full article

Incorporating antioxidants into cosmetics is the mainstay for developing new products to mitigate skin aging. However, identifying novel multifunctional antioxidant ingredients with additional relevant properties that block the skin hallmarks of aging is a very striking strategy. Many natural compounds, including xanthones, have demonstrated biologically notable properties. In particular, 1,2-dihydroxy-9H-xanthen-9-one (1,2-DHX) has inhibitory activity against skin enzymes, and metal-chelating and radical-scavenging activities. Therefore, 1,2-DHX is an attractive molecule for cosmetic purposes. With this goal in mind, the anti-inflammatory, antioxidant, and anti-allergic potentials of 1,2-DHX were investigated. 1,2-DHX demonstrated anti-inflammatory properties by inhibiting the synthesis of specific pro-inflammatory mediators, including interleukin-6 (IL-6) and prostaglandin E2 (PGE2), in human macrophages. This xanthone did not elicit sensitization reactions and did inhibit allergic reactions triggered by a strong skin allergen, suggesting its potential as an anti-allergic compound. 1,2-DHX also revealed mitochondrial antioxidant activity by mitigating rotenone-induced oxidative stress in macrophages by up to 40%. Overall, 1,2-DHX displayed a safety profile and noteworthy biological activities, highlighting its multifunctional profile as an active cosmetic ingredient with anti-inflammatory, antioxidant, and anti-allergic properties. Full article

Background/Objectives: Essential oils (EOs) from Citrus species have attracted attention for their diverse properties, including anti-inflammatory, antioxidant and cytotoxic effects, which address critical health challenges such as chronic diseases and skin disorders. Citrus sinensis (L.) Osbeck, which is a widely cultivated citrus fruit, is attracting increasing attention in the field of medicinal research due to its richness of limonene (comprising approximately 85–90% of the oil). This study investigates the chemical profile of CS-EO and biological activities of CS-EO and limonene. Methods and Results: This study used gas chromatography–mass spectrometry (GC-MS), confirming limonene as the predominant compound (70.15%) along with other minor constituents, including thujene (10.52%), myrcene (5.54%) and α-pinene (2.81%). The biological activities of CS-EO and limonene were examined, specifically focusing on their antioxidant, anti-inflammatory, cytotoxicity and dermatoprotective effects. Antioxidant potential was evaluated using DPPH, FRAP and beta-carotene assays, with CS-EO and limonene exhibiting comparable efficacy. Anti-inflammatory properties were assessed via inhibition assays of prostaglandin E2 (PGE2) and nitric oxide (NO) production, showing significant reductions in LPS-stimulated macrophages treated by CS-EO or limonene. Cytotoxicity testing on various cell lines indicated selective activity of the tested compounds, with low toxicity observed on human skin fibroblasts. Limonene and CS-EO were highly effective on HepG2 cellules, with IC₅₀ values of 0.55 ± 0.01 µg/mL and 15.97 ± 1.20 µg/mL, respectively. Dermatoprotective effects were further confirmed using enzymes, where CS-EO and limonene showed remarkable inhibitory potential against elastase (IC₅₀ of 65.72 ± 1.92 and 86.07 ± 1.53 µg/mL, respectively) and tyrosinase (IC₅₀ of 102 ± 2.16 and 78.34 ± 1.15 µg/mL, respectively) enzymes compared to quercetin used as a standard (IC₅₀ of 111.03 ± 0.1 and 124.22 ± 0.07 µg/mL, respectively). Conclusions: The findings of this study suggest the potential for the development of new therapeutic approaches based on CS-EO, which could be applicable in the pharmaceutical, cosmetic and nutraceutical fields and have protective benefits for skin health. Full article

Background/Objectives: The therapeutic management of melanoma, the most aggressive form of skin cancer, remains challenging. In the search for more effective therapeutic options, metal-based complexes are being investigated for their anticancer properties. Cisplatin was the first clinically approved platinum-based drug and, based on its success, other metals (e.g., gold) are being used to design novel compounds. Methods: the antimelanoma potential of a new organometallic cyclometalated Au(III) complex [[Au(C^NOxN)Cl₂] (C^NOxN = 2-(phenyl-(2-pyridinylmethylene)aminoxy acetic acid))] (ST004) was evaluated in vitro and in vivo. Furthermore, the gold-based complex was incorporated in liposomes to overcome solubility and stability problems, to promote accumulation at melanoma sites and to maximize the therapeutic effect while controlling its reactivity. The antiproliferative activity of ST004 formulations was assessed in murine (B16F10) and human (A375 and MNT-1) melanoma cell lines after 24 and 48 h incubation periods. The proof-of-concept of the antimelanoma properties of ST004 formulations was carried out in subcutaneous and metastatic murine melanoma models. Results: the developed liposomal formulations showed a low mean size (around 100 nm), high homogeneity (with a low polydispersity index) and high incorporation efficiency (51 ± 15%). ST004 formulations exhibited antiproliferative activity with EC₅₀ values in the μmolar range being cell-line- and incubation-period-dependent. On the opposite side, the benchmark antimelanoma compound, dacarbazine (DTIC), presented an EC₅₀ > 100 μM. Cell cycle analysis revealed an arrest in G0/G1 phase for Free-ST004 in all cell lines. In turn, LIP-ST004 led to a G0/G1 halt in B16F10, and to an arrest in S phase in A375 and MNT-1 cells. Preliminary mechanistic studies in human red blood cells suggest that gold-based inhibition of glycerol permeation acts through aquaglyceroporin 3 (AQP3). In a metastatic murine melanoma, a significant reduction in lung metastases in animals receiving LIP-ST004, compared to free gold complex and DTIC, was observed. Conclusion: This study highlights the antimelanoma potential of a new gold-based complex. Additional studies, namely in vivo biodistribution profile and therapeutic validation of this organogold complex in other melanoma models, are expected to be performed in further investigations. Full article

Skin aging is intrinsic and extrinsic. Intrinsic, or chronological, skin aging is an inevitable process of chronological and physiological alterations. The factors contributing to extrinsic skin aging involve sunlight, nutrients, and stress. Thus, extrinsic aging is thought to be superimposed over intrinsic aging and depends on the intensity and duration of environmental exposure and skin type (e.g., dry skin, oily skin, or eczema). The most significant extrinsic aging factor is UV radiation, which causes cellular senescence in a process known as photoaging. This study aimed to illuminate the mechanism whereby solubilized elastin peptide lotion (EL) from the bulbus arteriosus of yellowtail (Seriola quinqueradiata) prevents skin photoaging in hairless mice. EL reduced wrinkle formation, epidermal skin thickness, and Ki67 (cell growth marker) mRNA expression in skin tissues from ultraviolet B (UVB)-irradiated mice. EL treatment also reduced glyoxalase-1 (key enzyme of glucose metabolism) levels in skin tissue. Although no significant differences in collagen and elastin contents were found in dermal areas, matrix metalloproteinase-12 (wrinkle-related marker) expression was reduced following EL application. Furthermore, skin DPP-IV/CD26 (new senescence marker) levels decreased following EL treatment in photoaging model mice. These results suggest that EL moderates skin damage caused by UVB irradiation by regulating senescence-related molecule expression. Full article

Satellite-retrieved sea-surface skin temperature (SST_skin) is essential for many Near-Real-Time studies. This study aimed to assess the potential to improve the accuracy of satellite-based SST_skin retrieval in the Caribbean region by using atmospheric correction algorithms based on four readily available machine learning (ML) approaches: eXtreme Gradient Boosting (XGBoost), Support Vector Regression (SVR), Random Forest (RF), and the Artificial Neural Network (ANN). The ML models were trained on an extensive dataset comprising in situ SST measurements and atmospheric state parameters obtained from satellite products, reanalyzed datasets, research cruises, surface moorings, and drifting buoys. The benefits and shortcomings of various ML methods were assessed through comparisons with withheld in situ measurements. The results demonstrate that the ML-based algorithms achieve promising accuracy, with mean biases within 0.07 K when compared with the buoy data and ranging from −0.107 K to 0.179 K relative to the ship-derived SST_skin data. Notably, both XGBoost and RF stand out for their superior correlation and efficacy in the statistical results of validation. The improved SST_skin derived using the ML-based algorithms could enhance our understanding of vital oceanic and atmospheric characteristics and have the potential to reduce uncertainty in oceanographic, meteorological, and climate research. Full article