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1.
Sci Rep ; 14(1): 10618, 2024 05 09.
Article En | MEDLINE | ID: mdl-38724594

Various kinds of pets have been known to contract the ectoparasite Sarcoptes scabiei. Current acaricides are becoming less effective because of the resistance developed by the mite besides their adverse effects on the general activity and reproductive performance of domestic pets. For this reason, the present study aims to discover a novel and safe approach using silver and gold nanoparticles to fight Sarcoptic mange in rabbits as well as to explain their mechanism of action. 15 pet rabbits with clinical signs of Sarcoptic mange that were confirmed by the microscopic examination were used in our study. All rabbits used in this study were assessed positive for the presence of different developing stages of S. scabiei. Three groups of rabbits (n = 5) were used as follows: group (1) didn't receive any treatment, and group (2 and 3) was treated with either AgNPs or GNPs, respectively. Both nanoparticles were applied daily on the affected skin areas via a dressing and injected subcutaneously once a week for 2 weeks at a dose of 0.5 mg/kg bwt. Our results revealed that all rabbits were severely infested and took a mean score = 3. The skin lesions in rabbits that didn't receive any treatments progressed extensively and took a mean score = of 4. On the other hand, all nanoparticle-treated groups displayed marked improvement in the skin lesion and took an average score of 0-1. All NPs treated groups showed remarkable improvement in the microscopic pictures along with mild iNOS, TNF-α, and Cox-2 expression. Both nanoparticles could downregulate the m-RNA levels of IL-6 and IFγ and upregulate IL-10 and TGF-1ß genes to promote skin healing. Dressing rabbits with both NPs didn't affect either liver and kidney biomarkers or serum Ig levels indicating their safety. Our residual analysis detected AgNPs in the liver of rabbits but did not detect any residues of GNPs in such organs. We recommend using GNPs as an alternative acaricide to fight rabbit mange.


Gold , Metal Nanoparticles , Sarcoptes scabiei , Scabies , Silver , Animals , Rabbits , Metal Nanoparticles/chemistry , Metal Nanoparticles/administration & dosage , Gold/chemistry , Scabies/drug therapy , Scabies/parasitology , Silver/chemistry , Sarcoptes scabiei/drug effects , Skin/drug effects , Skin/parasitology , Skin/pathology , Skin/metabolism
2.
Int J Mol Sci ; 25(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38731954

Natural products have many healing effects on the skin with minimal or no adverse effects. In this study, we analyzed the regenerative properties of a waste product (hydrolate) derived from Helichrysum italicum (HH) on scratch-tested skin cell populations seeded on a fluidic culture system. Helichrysum italicum has always been recognized in the traditional medicine of Mediterranean countries for its wide pharmacological activities. We recreated skin physiology with a bioreactor that mimics skin stem cell (SSCs) and fibroblast (HFF1) communication as in vivo skin layers. Dynamic culture models represent an essential instrument for recreating and preserving the complex multicellular organization and interactions of the cellular microenvironment. Both cell types were exposed to two different concentrations of HH after the scratch assay and were compared to untreated control cells. Collagen is the constituent of many wound care products that act directly on the damaged wound environment. We analyzed the role played by HH in stimulating collagen production during tissue repair, both in static and dynamic culture conditions, by a confocal microscopic analysis. In addition, we performed a gene expression analysis that revealed the activation of a molecular program of stemness in treated skin stem cells. Altogether, our results indicate a future translational application of this natural extract to support skin regeneration and define a new protocol to recreate a dynamic process of healing.


Collagen , Helichrysum , Plant Extracts , Regeneration , Skin , Wound Healing , Wound Healing/drug effects , Collagen/metabolism , Humans , Skin/metabolism , Skin/drug effects , Helichrysum/chemistry , Plant Extracts/pharmacology , Regeneration/drug effects , Fibroblasts/metabolism , Fibroblasts/drug effects , Stem Cells/metabolism , Stem Cells/drug effects , Stem Cells/cytology , Cells, Cultured
3.
Int J Mol Sci ; 25(9)2024 Apr 27.
Article En | MEDLINE | ID: mdl-38731982

Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained in dogwood extracts of different fruit colors (yellow, red, and dark ruby red) prepared using different extractants was investigated. These analyses were performed using a Franz chamber and HPLC-UV chromatography. Moreover, the antioxidant properties of the tested extracts were compared and their impact on the intracellular level of free radicals in skin cells was assessed. The cytotoxicity of these extracts towards keratinocytes and fibroblasts was also analyzed and their anti-inflammatory properties were assessed using the enzyme-linked immunosorbent assay (ELISA). The analyses showed differences in the penetration of individual phenolic acids into the skin and different biological activities of the tested extracts. None of the extracts had cytotoxic effects on skin cells in vitro, and the strongest antioxidant and anti-inflammatory properties were found in dogwood extracts with dark ruby red fruits.


Anti-Inflammatory Agents , Antioxidants , Cornus , Plant Extracts , Skin , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cornus/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Skin/metabolism , Skin/drug effects , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Hydroxybenzoates/pharmacology , Hydroxybenzoates/chemistry , Fruit/chemistry , Animals , Chromatography, High Pressure Liquid
4.
Adv Exp Med Biol ; 1447: 117-129, 2024.
Article En | MEDLINE | ID: mdl-38724789

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.


Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/microbiology , Administration, Topical , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Phosphodiesterase 4 Inhibitors/therapeutic use , Administration, Cutaneous , Skin/drug effects , Skin/microbiology , Skin/pathology , Calcineurin Inhibitors/therapeutic use , Calcineurin Inhibitors/administration & dosage , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Dermatologic Agents/adverse effects
5.
Lipids Health Dis ; 23(1): 138, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734619

BACKGROUND: Skin barrier alterations play a crucial function in melasma development. Past researches have demonstrated variations in lipid content between the epidermis of melasma lesions and normal tissues, along with the varied expression of lipid-related genes in melasma. This study aimed to analyze the lipidome profiles of skin surface lipids (SSL) in patients with melasma before and after treatment to understand associated abnormalities. METHODS: Melasma was treated with tranexamic acid orally and hydroquinone cream topically. Disease was assessed using the Melasma Area and Severity Index (MASI), and the impact to life was evaluated with Melasma Quality of Life (MELASQoL) score. Epidermal melanin particles were observed using reflection confocal microscopy (RCM), whereas epidermal pigment and blood vessel morphology were observed using dermoscopy, and SSL samples were collected. Specific information regarding alterations in lipid composition was obtained through multivariate analysis of the liquid chromatography-mass spectrometry data. RESULTS: After treatment, patients with melasma exhibited decreased MASI and MELASQoL scores (P < 0.001); RCM revealed reduced melanin content in the lesions, and dermoscopy revealed fewer blood vessels. Fifteen lipid subclasses and 382 lipid molecules were identified using lipidomic assays. The expression levels of total lipids, phosphatidylcholine, and phosphatidylethanolamine in the melasma lesions decreased after treatment (P < 0.05). CONCLUSION: This study revealed alterations in the SSL composition after effective melasma treatment, suggesting a compensatory role for lipids in melasma barrier function. The mechanism involving SSL and the lipid barrier, which influences melasma's occurrence, needs further elucidation.


Hydroquinones , Lipidomics , Melanosis , Quality of Life , Humans , Melanosis/drug therapy , Female , Adult , Hydroquinones/therapeutic use , Hydroquinones/administration & dosage , Tranexamic Acid/therapeutic use , Middle Aged , Melanins/metabolism , Male , Lipids/blood , Lipids/analysis , Epidermis/metabolism , Epidermis/drug effects , Epidermis/pathology , Phosphatidylethanolamines/metabolism , Phosphatidylcholines/metabolism , Skin/pathology , Skin/drug effects , Skin/metabolism , Lipid Metabolism/drug effects
6.
AAPS PharmSciTech ; 25(5): 112, 2024 May 14.
Article En | MEDLINE | ID: mdl-38744715

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.


Administration, Cutaneous , Etodolac , Skin Absorption , Skin , Animals , Etodolac/administration & dosage , Etodolac/pharmacokinetics , Etodolac/chemistry , Rats , Mice , Skin Absorption/physiology , Skin/metabolism , Skin/drug effects , Male , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Acute Pain/drug therapy , Chemistry, Pharmaceutical/methods , Permeability , Rats, Sprague-Dawley , Drug Compounding/methods
7.
Skin Res Technol ; 30(5): e13727, 2024 May.
Article En | MEDLINE | ID: mdl-38711343

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.


Cuminum , Plant Extracts , Rats, Sprague-Dawley , Seeds , Wound Healing , Animals , Wound Healing/drug effects , Seeds/chemistry , Rats , Plant Extracts/pharmacology , Cuminum/chemistry , Male , Skin/injuries , Skin/drug effects , Skin/pathology , Transforming Growth Factor beta1/metabolism
8.
J Drugs Dermatol ; 23(5): 366-375, 2024 May 01.
Article En | MEDLINE | ID: mdl-38709706

OBJECTIVE:   This study aimed to investigate the ultraviolet (UV) protection/repair benefits of a patented Amino Acid Complex (AAComplex). METHODS: I) AAComplex was incubated with dermal fibroblasts, with/without UVA, and collagen I was measured with a GlasBoxPlus device. II) A lotion, with/without AAComplex (1%) was applied topically to skin explants, following UVA irradiation, and quantified for health-related biomarkers (TNFalpha, histamine, and MMP-1). III) A broad spectrum sunscreen with SPF 46 and a skincare serum containing AAComplex (2%) were assessed using epidermal equivalents, in the presence of UV irradiation, for effects on IL-1alpha, thymine dimers, Ki-67, filaggrin and Nrf2. RESULTS: I) Collagen I synthesis in dermal fibroblasts was significantly decreased after UVA compared to without UV. The presence of AAComplex prevented this decrease. II) UVA irradiation of skin explants increased histamine, TNFα, and MMP-1. Hydrocortisone aceponate cream significantly decreases all 3 biomarkers. AAComplex contained lotion also significantly decreased all 3 biomarkers, the no AAComplex control lotion only reduced histamine. III) With the regimen of sunscreen + AAComplex contained skincare serum, the significant reduction in IL-1alpha was observed along with a complete recovery of Ki-67 and stimulation of filaggrin and Nrf2T. No thymine dimer positive cell was observed indicating the most positive skin impact from the regiment.  Conclusion: This research using different human skin models demonstrated that AAComplex can provide protection and damage repair caused by UV, at the ingredient level also when formulated in a serum or lotion formula. Skin may be best protected from UV damage when the regimen is used.   J Drugs Dermatol. 2024;23(5):366-375. doi:10.36849/JDD.7916.


Fibroblasts , Filaggrin Proteins , Matrix Metalloproteinase 1 , NF-E2-Related Factor 2 , Tumor Necrosis Factor-alpha , Ultraviolet Rays , Humans , Ultraviolet Rays/adverse effects , Fibroblasts/drug effects , Fibroblasts/radiation effects , Fibroblasts/metabolism , Matrix Metalloproteinase 1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Skin/radiation effects , Skin/drug effects , Skin/metabolism , Sunscreening Agents/administration & dosage , Sunscreening Agents/chemistry , Sunscreening Agents/pharmacology , Amino Acids/administration & dosage , Amino Acids/pharmacology , Amino Acids/chemistry , Interleukin-1alpha/metabolism , Histamine/blood , Skin Cream/administration & dosage , Biomarkers/metabolism , Collagen Type I , Intermediate Filament Proteins/metabolism , Ki-67 Antigen/metabolism , Pyrimidine Dimers , Cells, Cultured
9.
J Drugs Dermatol ; 23(5): 360-365, 2024 May 01.
Article En | MEDLINE | ID: mdl-38709707

BACKGROUND: The use of ointments can be beneficial for dry, chapped, or cracked skin and also for supporting wound healing. We describe the results of 2 studies with an over-the-counter healing ointment (HO) to evaluate the effects on skin hydration and in the setting of wound healing after dermatologic procedures.  Methods: Study 1 was a single-center, in-use study using HO on qualified areas at least once daily for 4 weeks in subjects with dry, cracked body skin and self-perceived sensitive skin. Study 2 was a multi-center study of wound healing in subjects using HO on a daily basis after having dermatologic surgical procedures.  Results: In Study 1, there was a significant reduction in skin dryness after 1 and 4 weeks of HO use (P<0.05). Image analysis of the skin revealed a significant increase in skin smoothness after the first application of HO in 100% of subjects (P<0.05). Tolerability and safety were excellent, and HO was well-perceived by subjects throughout the study. In Study 2, HO improved clinical assessments at all time points compared with baseline with a decrease in erythema, edema, scabbing/crusting, and an improvement in overall wound appearance (P<0.05). There was no worsening or significant increase in measures for tolerability parameters at any study visits. Additionally, HO achieved a favorable perception by study subjects.  Conclusions: HO has a well-established safety profile and has been shown to improve both skin hydration and the overall wound healing process after dermatologic surgical procedures. J Drugs Dermatol. 2024;23(5):360-365. doi:10.36849/JDD.8224.


Nonprescription Drugs , Ointments , Wound Healing , Humans , Wound Healing/drug effects , Female , Male , Middle Aged , Adult , Nonprescription Drugs/administration & dosage , Aged , Treatment Outcome , Skin Diseases/drug therapy , Skin/drug effects , Skin/pathology , Dermatologic Surgical Procedures/adverse effects , Young Adult , Administration, Cutaneous
10.
Sci Rep ; 14(1): 10193, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702361

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.


Amphibians , Arsenic , Microbiota , Skin , Animals , Arsenic/metabolism , Arsenic/toxicity , Microbiota/drug effects , Skin/microbiology , Skin/drug effects , Skin/metabolism , Amphibians/microbiology , Bacteria/drug effects , Bacteria/classification , Bacteria/metabolism , Bacteria/genetics , Permeability/drug effects
11.
AAPS PharmSciTech ; 25(5): 101, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714629

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.


Administration, Cutaneous , Drug Liberation , Niacin , Polysaccharides , Rats, Wistar , Skin Absorption , Skin , Animals , Rats , Niacin/administration & dosage , Niacin/chemistry , Niacin/pharmacology , Polysaccharides/chemistry , Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Skin/metabolism , Skin/drug effects , Skin Absorption/drug effects , Flushing/chemically induced , Tensile Strength , Male , Drug Delivery Systems/methods , Tamarindus/chemistry , Polymers/chemistry
12.
Arthritis Res Ther ; 26(1): 94, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702742

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and inflammation, followed by excessive fibrosis of the skin and other internal organs, including the lungs. CX3CL1 (fractalkine), a chemokine expressed on endothelial cells, supports the migration of macrophages and T cells that express its specific receptor CX3CR1 into targeted tissues. We previously reported that anti-CX3CL1 monoclonal antibody (mAb) treatment significantly inhibited transforming growth factor (TGF)-ß1-induced expression of type I collagen and fibronectin 1 in human dermal fibroblasts. Additionally, anti-mouse CX3CL1 mAb efficiently suppressed skin inflammation and fibrosis in bleomycin- and growth factor-induced SSc mouse models. However, further studies using different mouse models of the complex immunopathology of SSc are required before the initiation of a clinical trial of CX3CL1 inhibitors for human SSc. METHODS: To assess the preclinical utility and functional mechanism of anti-CX3CL1 mAb therapy in skin and lung fibrosis, a sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) mouse model was analyzed with immunohistochemical staining for characteristic infiltrating cells and RNA sequencing assays. RESULTS: On day 42 after bone marrow transplantation, Scl-cGVHD mice showed increased serum CX3CL1 level. Intraperitoneal administration of anti-CX3CL1 mAb inhibited the development of fibrosis in the skin and lungs of Scl-cGVHD model, and did not result in any apparent adverse events. The therapeutic effects were correlated with the number of tissue-infiltrating inflammatory cells and α-smooth muscle actin (α-SMA)-positive myofibroblasts. RNA sequencing analysis of the fibrotic skin demonstrated that cGVHD-dependent induction of gene sets associated with macrophage-related inflammation and fibrosis was significantly downregulated by mAb treatment. In the process of fibrosis, mAb treatment reduced cGVHD-induced infiltration of macrophages and T cells in the skin and lungs, especially those expressing CX3CR1. CONCLUSIONS: Together with our previous findings in other SSc mouse models, the current results indicated that anti-CX3CL1 mAb therapy could be a rational therapeutic approach for fibrotic disorders, such as human SSc and Scl-cGVHD.


Antibodies, Monoclonal , Chemokine CX3CL1 , Disease Models, Animal , Graft vs Host Disease , Pulmonary Fibrosis , Scleroderma, Systemic , Skin , Animals , Graft vs Host Disease/drug therapy , Graft vs Host Disease/immunology , Graft vs Host Disease/pathology , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/pathology , Scleroderma, Systemic/immunology , Mice , Chemokine CX3CL1/metabolism , Chemokine CX3CL1/antagonists & inhibitors , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/prevention & control , Skin/pathology , Skin/drug effects , Skin/metabolism , Skin/immunology , Fibrosis , Female , Mice, Inbred C57BL , Humans , Lung/pathology , Lung/drug effects , Lung/metabolism , Lung/immunology
13.
Pediatr Allergy Immunol ; 35(5): e14130, 2024 May.
Article En | MEDLINE | ID: mdl-38693814

While the early introduction of food allergens in the infant diet has been shown to be effective at preventing the development of food allergy (FA), its implementation in real life has been associated with various challenges. Interventions aimed at correcting skin barrier dysfunction have been explored in recent decades as a distinct or complementary mean to prevent allergic sensitization through the skin and subsequent development of FA. Studies assessing the application of emollient from birth have yielded conflicting results, and meta-analyses have demonstrated either no effect or only a slight positive effect on FA prevention. However, a careful review of the clinical trials reveals that different emollients were used, which may have explained some of the discrepancies between study results. Emollient application protocols also varied widely between studies. While firm conclusions cannot be drawn with regard to their overall efficacy at preventing FA, the available data provide valuable insight into the characteristics that could be associated with a more effective intervention. Namely, successful trials tended to use emollients with an acidic pH of 5.5, applied over the entire body, and combined with topical corticosteroids in affected areas. Consensus on the optimal strategy to restore skin barrier function could help improve the homogeneity and clinical relevance of future trials on this topic. In the meantime, clinicians should avoid products associated with worse outcomes.


Emollients , Food Hypersensitivity , Skin , Humans , Food Hypersensitivity/prevention & control , Emollients/administration & dosage , Skin/drug effects , Skin/immunology , Infant , Allergens/immunology , Allergens/administration & dosage , Clinical Trials as Topic , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Infant, Newborn
14.
Arch Dermatol Res ; 316(5): 162, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734848

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.


Acitretin , Nerve Tissue Proteins , Psoriasis , Severity of Illness Index , Humans , Psoriasis/genetics , Psoriasis/drug therapy , Psoriasis/diagnosis , Male , Female , Adult , Nerve Tissue Proteins/genetics , Middle Aged , Acitretin/therapeutic use , Acitretin/administration & dosage , Ultraviolet Therapy/methods , Single-Blind Method , Polymorphism, Single Nucleotide , Young Adult , Skin/pathology , Skin/metabolism , Skin/drug effects , Receptors, Immunologic/genetics , Treatment Outcome , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Keratolytic Agents/therapeutic use , Keratolytic Agents/administration & dosage , Combined Modality Therapy
15.
Int J Nanomedicine ; 19: 4061-4079, 2024.
Article En | MEDLINE | ID: mdl-38736651

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.


Administration, Cutaneous , Cannabidiol , Needles , Particle Size , Rats, Sprague-Dawley , Skin Absorption , Suspensions , Animals , Cannabidiol/pharmacokinetics , Cannabidiol/administration & dosage , Cannabidiol/chemistry , Skin Absorption/drug effects , Rats , Suspensions/chemistry , Male , Skin/metabolism , Skin/drug effects , Solubility , Drug Delivery Systems/methods , Transdermal Patch , Nanoparticles/chemistry , Microinjections/methods , Microinjections/instrumentation
16.
Int J Mol Sci ; 25(9)2024 May 03.
Article En | MEDLINE | ID: mdl-38732212

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.


Cell Differentiation , Cell Movement , Keratinocytes , Magnesium , Matrix Metalloproteinase 7 , Wound Healing , Wound Healing/drug effects , Humans , Cell Movement/drug effects , Keratinocytes/drug effects , Keratinocytes/metabolism , Cell Differentiation/drug effects , Magnesium/pharmacology , Magnesium/metabolism , Matrix Metalloproteinase 7/metabolism , Matrix Metalloproteinase 7/genetics , Skin/metabolism , Skin/drug effects , Skin/injuries , MAP Kinase Signaling System/drug effects , Cell Line , Epidermis/drug effects , Epidermis/metabolism , Magnesium Chloride/pharmacology
17.
ACS Nano ; 18(19): 12341-12354, 2024 May 14.
Article En | MEDLINE | ID: mdl-38695772

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.


Nanofibers , Animals , Rats , Nanofibers/chemistry , Wound Healing/drug effects , Reactive Oxygen Species/metabolism , Skin/drug effects , Skin/pathology , Tissue Adhesions/prevention & control , Rats, Sprague-Dawley , Cell Adhesion/drug effects , Cerium/chemistry , Cerium/pharmacology , Surface Properties , Mice , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
18.
Molecules ; 29(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38731413

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1ß, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.


Arbutin , Skin Aging , Ultraviolet Rays , Arbutin/pharmacology , Ultraviolet Rays/adverse effects , Animals , Skin Aging/drug effects , Skin Aging/radiation effects , Mice , Monophenol Monooxygenase/metabolism , Monophenol Monooxygenase/antagonists & inhibitors , Humans , Skin/radiation effects , Skin/drug effects , Skin/metabolism , Skin/pathology
19.
Molecules ; 29(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38731569

Skin wounds, leading to infections and death, have a huge negative impact on healthcare systems around the world. Antibacterial therapy and the suppression of excessive inflammation help wounds heal. To date, the application of wound dressings, biologics and biomaterials (hydrogels, epidermal growth factor, stem cells, etc.) is limited due to their difficult and expensive preparation process. Cinnamomum burmannii (Nees & T. Nees) Blume is an herb in traditional medicine, and its essential oil is rich in D-borneol, with antibacterial and anti-inflammatory effects. However, it is not clear whether Cinnamomum burmannii essential oil has the function of promoting wound healing. This study analyzed 32 main components and their relative contents of essential oil using GC-MS. Then, network pharmacology was used to predict the possible targets of this essential oil in wound healing. We first proved this essential oil's effects in vitro and in vivo. Cinnamomum burmannii essential oil could not only promote the proliferation and migration of skin stromal cells, but also promote M2-type polarization of macrophages while inhibiting the expression of pro-inflammatory cytokines. This study explored the possible mechanism by which Cinnamomum burmannii essential oil promotes wound healing, providing a cheap and effective strategy for promoting wound healing.


Cinnamomum , Oils, Volatile , Wound Healing , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Wound Healing/drug effects , Cinnamomum/chemistry , Animals , Mice , Cell Proliferation/drug effects , Cytokines/metabolism , Macrophages/drug effects , Macrophages/metabolism , Cell Movement/drug effects , Skin/drug effects , Humans
20.
Molecules ; 29(9)2024 May 02.
Article En | MEDLINE | ID: mdl-38731597

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant Artemisia annua L. is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria. A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia teas reduced fibroblast viability 4 d post-treatment in up to 80% of their respective controls. After 4 d of treatment, AS DHA and Artemisia teas downregulated ACTA2 up to 10 fold while ART had no significant effect, and AM increased viability by 10%. MMP1 and MMP3 were upregulated by AS, 17.5 and 32.6 fold, respectively, and by DHA, 8 and 51.8 fold, respectively. ART had no effect, but A. annua and A. afra teas increased MMP3 5 and 16-fold, respectively. Although A. afra tea increased COL3A1 5 fold, MMP1 decreased >7 fold with no change in either transcript by A. annua tea. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone but was less effective than A. afra. Immunofluorescent staining for smooth-muscle α-actin (α-SMA) correlated well with the transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts, with evidence also of remodeling of fibrotic ECM.


Artemisia , Artemisinins , Fibroblasts , Fibrosis , Humans , Artemisinins/pharmacology , Fibroblasts/drug effects , Fibroblasts/metabolism , Artemisia/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Cell Survival/drug effects , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinase 3/genetics , Actins/metabolism , Actins/genetics , Artesunate/pharmacology , Gene Expression Regulation/drug effects , Artemether/pharmacology , Skin/drug effects , Skin/metabolism , Skin/pathology
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