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1.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806904

RESUMEN

This study was conducted to compare the effects of commercially available (C) and green synthesized (GS) Zinc oxide nanoparticles (ZnO-NPs) on immunological responses of common carp (Cyprinus carpio) skin mucus. GS ZnO-NPs were generated using Thymus pubescent and characterized by UV-vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). Fish (n = 150) were randomly allocated into five groups in triplicate and received a waterborne concentration of 0% (control), 25%, and 50% of LC50 96 h of commercially available (C1 and C2) and green synthesized ZnO-NPs (GS1 and GS2) for 21 days. Results from XRD displayed ZnO-NPs with 58 nm in size and UV-vis DRS, EDX, and FT-IR analysis showed that some functional groups from plant extract bonded to the surface of NPs. The SEM images showed that ZnO-NPs have conical morphology. Acute toxicity study showed a higher dose of LC5096h for green synthesized ZnO-NPs (78.9 mg.L-1) compared to the commercial source (59.95 mg.L-1). The highest activity of lysozyme and alternative complement activity (ACH50) were found in control and GS1 groups. A significant decrease in alkaline phosphatase activity (ALP) was found in C1 and C2 groups compared to other treatments. Protease activity (P) was significantly decreased in the C2 group compared to the control and GS groups. Total immunoglobulin (total Ig) content was the highest in the control. In addition, total Ig in the GS1 group was higher than GS2. The exposure to ZnO-NPs lowered total protein content in all experimental groups when compared to control. Present findings revealed lower induced immunosuppressive effects by green synthesized ZnO-NPs on key parameters of fish skin mucus.


Asunto(s)
Carpas/fisiología , Factores Inmunológicos/síntesis química , Factores Inmunológicos/farmacología , Nanopartículas del Metal/química , Moco/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Óxido de Zinc/química , Animales , Técnicas de Química Sintética , Tecnología Química Verde , Nanopartículas del Metal/ultraestructura , Análisis Espectral
2.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806685

RESUMEN

Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the KIT proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.


Asunto(s)
Mastocitosis Cutánea/diagnóstico , Mastocitosis Cutánea/tratamiento farmacológico , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/tratamiento farmacológico , Niño , Epinefrina/farmacología , Antagonistas de los Receptores Histamínicos H1/farmacología , Antagonistas de los Receptores Histamínicos H2/farmacología , Humanos , Mastocitos/efectos de los fármacos , Piel/efectos de los fármacos
3.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799554

RESUMEN

In the skin care field, bacterial nanocellulose (BNC), a versatile polysaccharide produced by non-pathogenic acetic acid bacteria, has received increased attention as a promising candidate to replace synthetic polymers (e.g., nylon, polyethylene, polyacrylamides) commonly used in cosmetics. The applicability of BNC in cosmetics has been mainly investigated as a carrier of active ingredients or as a structuring agent of cosmetic formulations. However, with the sustainability issues that are underway in the highly innovative cosmetic industry and with the growth prospects for the market of bio-based products, a much more prominent role is envisioned for BNC in this field. Thus, this review provides a comprehensive overview of the most recent (last 5 years) and relevant developments and challenges in the research of BNC applied to cosmetic, aiming at inspiring future research to go beyond in the applicability of this exceptional biotechnological material in such a promising area.


Asunto(s)
Bacterias/química , Celulosa/farmacología , Cosméticos/química , Tecnología Química Verde , Polisacáridos Bacterianos/farmacología , Celulosa/química , Celulosa/aislamiento & purificación , Cosméticos/farmacología , Humanos , Nanoestructuras/química , Nanoestructuras/ultraestructura , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/aislamiento & purificación , Piel/efectos de los fármacos , Cuidados de la Piel/métodos
4.
Molecules ; 26(6)2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33803643

RESUMEN

Unprotected exposure of skin to solar ultraviolet radiation (UVR) may damage the DNA of skin cells and can lead to skin cancer. Sunscreens are topical formulations used to protect skin against UVR. The active ingredients of sunscreens are UV filters that absorb, scatter, and/or reflect UVR. Preventing the formation of free radicals and repairing DNA damages, natural antioxidants are also added to sunscreens as a second fold of protection against UVR. Antioxidants can help stabilise these formulations during the manufacturing process and upon application on skin. However, UV filters and antioxidants are both susceptible to degradation upon exposure to sunlight and oxygen. Additionally, due to their poor water solubility, natural antioxidants are challenging to formulate and exhibit limited penetration and bioavailability in the site of action (i.e., deeper skin layers). Cyclodextrins (CDs) are cyclic oligosaccharides that are capable of forming inclusion complexes with poorly soluble drugs, such as antioxidants. In this review, we discuss the use of CDs inclusion complexes to enhance the aqueous solubility of antioxidants and chemical UV filters and provide a protective shield against degradative factors. The role of CDs in providing a controlled drug release profile from sunscreens is also discussed. Finally, incorporating CDs inclusion complexes into sunscreens has the potential to increase their efficiency and hence improve their skin cancer prevention.


Asunto(s)
Ciclodextrinas/farmacología , Neoplasias Cutáneas/prevención & control , Protectores Solares/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Ciclodextrinas/administración & dosificación , Ciclodextrinas/química , Daño del ADN , Preparaciones de Acción Retardada , Composición de Medicamentos , Estabilidad de Medicamentos , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Humanos , Estructura Molecular , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Solubilidad , Protectores Solares/administración & dosificación , Protectores Solares/química , Rayos Ultravioleta/efectos adversos
5.
Molecules ; 26(6)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33809637

RESUMEN

Skin aging occurs inevitably as a natural result of physiological changes over time. In particular, solar exposure of the skin accounts for up to 90% of skin damage. Numerous studies have examined the ability of dietary constituents to prevent skin aging, and recent research has emphasized the role of functional probiotics in intestinal function and skin aging. However, the mechanism of the interactions between aging and probiotics has not been elucidated yet. The aim of this study was to determine the role of exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) identified as Lactobacillus plantarum HY7714 in regulating tight junctions in intestinal epithelial cells and increasing moisture retention in human dermal fibroblasts cells. We observed that HY7714 EPS controlled intestinal tight junctions in Caco-2 cells by upregulating the genes encoding occludin-1 (OCL-1) and zonula occluden-1 (ZO-1). In addition, HY7714 EPS effectively improved UVB-induced cytotoxicity and hydration capacity in HS68 cells by downregulating production of metalloproteinases (MMPs) and reactive oxygen species (ROS). In summary, HY7714 EPS is an effective anti-aging molecule in skin and may have therapeutic potential against skin diseases and UVB-induced damage. Therefore, HY7714 EPS serves as a functional substance in skin-gut axis communication.


Asunto(s)
Tracto Gastrointestinal/efectos de los fármacos , Lactobacillus plantarum/metabolismo , Polisacáridos/farmacología , Sustancias Protectoras/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Células CACO-2 , Línea Celular Tumoral , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Humanos , Ocludina/metabolismo , Probióticos/metabolismo , Piel/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo
6.
J Zoo Wildl Med ; 52(1): 117-125, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33827168

RESUMEN

The objective of this pilot study was to examine the histologic effects associated with three known sclerosing agents and their ability to induce fibrosis in the subcutaneous space between the cervicocephalic air sac and skin. In the future, these drugs may prove useful in treating birds experiencing cervicocephalic diverticula rupture. The agents used were 1% polidocanol, absolute ethanol, and doxycycline hyclate. Twelve healthy adult chickens (Gallus gallus domesticus) were used in this study. The chickens were randomly allocated into three groups denoting day of euthanasia (day 4, 7, or 14). On day 0, all agents were injected (0.2 ml) subcutaneously, in a four-point grid fashion, in both the cervical and pectoral region of each bird. After euthanasia, the skin and subcutaneous tissues corresponding to the injection sites were harvested for histologic assessment. Tissue sections were assessed for fibrosis and lymphocytic and histiocytic inflammation. A scoring system was established to rank sclerosing agents by fibrosing and inflammatory ability. In the cervical region of chickens, 1% polidocanol induced the greatest inflammatory changes by day 7. Data suggest that doxycycline hyclate may produce the greatest cutaneous and subcutaneous fibrosis overall among all groups of birds. No adverse reactions were associated with any injection. Sterile saline produced the least amount of inflammation when assessed with the scoring system. Further investigation is needed to determine the safety of injections of larger volume with these chemicals and whether these findings can be extrapolated to birds with disease.


Asunto(s)
Sacos Aéreos/patología , Pollos , Doxiciclina/farmacología , Etanol/farmacología , Polidocanol/farmacología , Animales , Doxiciclina/administración & dosificación , Quimioterapia Combinada , Etanol/administración & dosificación , Fibrosis/inducido químicamente , Fibrosis/veterinaria , Histiocitos , Inflamación/inducido químicamente , Inflamación/veterinaria , Linfocitos , Proyectos Piloto , Polidocanol/administración & dosificación , Enfermedades de las Aves de Corral/terapia , Rotura/terapia , Rotura/veterinaria , Soluciones Esclerosantes/administración & dosificación , Soluciones Esclerosantes/uso terapéutico , Piel/efectos de los fármacos , Piel/patología
7.
Medicine (Baltimore) ; 100(16): e25513, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33879687

RESUMEN

RATIONALE: Immune checkpoint inhibition has dramatically altered the therapeutic landscape in the treatment of a range of locally advanced and metastatic skin cancers. In particular, the treatment of metastatic melanoma with combined anti-programmed cell death protein 1 (anti-PD1) and anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) antagonists has resulted in median 5-year survival rates of over 50%. However, combined immune checkpoint inhibitor therapy frequently results in the development of immune-related adverse events (irAE) which can be severe and life-threatening. While the typical irAEs, namely colitis, thyroiditis, and hepatitis are well recognized, cutaneous irAEs are varied and can be difficult to accurately diagnose. PATIENT CONCERNS: A 61-year-old female with metastatic melanoma presented with widespread indurated, waxy skin changes, and weight loss following combined anti-PD1 and anti-CTLA4 immunotherapy. DIAGNOSES: Generalized morphea in the setting of combined immunotherapy. INTERVENTIONS: Dexamethasone pulse therapy (100 mg i.v. over 3 days) was combined with topical therapy (clobetasone propionate ointment) and physiotherapy. Four cycles of dexamethasone pulse therapy, at 4 weekly intervals, led to an improvement in the skin changes, accompanied by increased mobility. However, the changes did not resolve completely. OUTCOME: Staging examinations revealed progressive melanoma brain metastases and despite 2 further cycles of combined anti-PD1 and anti-CTLA4 immunotherapy followed by 1.5 cycles of Fotemustine, the patient died 22 months after the development of the scleroderma-like skin changes. LESSONS: Cutaneous irAEs are varied in nature and severity. Sclerotic skin changes are rare, but unlike cutaneous irAEs related to immune checkpoint inhibitor therapy, they are often refractory to standard treatment with systemic corticosteroids. Clinicians should be aware of immunotherapy-related scleroderma to prompt dermatological evaluation to facilitate early recognition and initiate treatment. Administration of systemic immunosuppression should be carefully balanced against the risk of promoting melanoma progression.


Asunto(s)
/efectos adversos , Melanoma/tratamiento farmacológico , Esclerodermia Sistémica/inmunología , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Terapia Combinada/métodos , Quimioterapia Combinada/métodos , Femenino , Glucocorticoides , Humanos , Melanoma/inmunología , Melanoma/secundario , Persona de Mediana Edad , Modalidades de Fisioterapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Quimioterapia por Pulso , Esclerodermia Sistémica/inducido químicamente , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/terapia , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Resultado del Tratamiento
8.
AAPS PharmSciTech ; 22(3): 117, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33768360

RESUMEN

This paper aimed to provide an insight into the mechanism of transdermal penetration of drug molecules with respect to their physicochemical properties, such as solubility (S), the presence of enantiomer (ET) and logarithm of octanol-water partition coefficient (log P), molecular weight (MW), and melting point (MP). Propionic acid derivatives were evaluated for their flux through full-thickness skin excised from hairless mice upon being delivered from silicone-based pressure-sensitive adhesive (PSA) matrices in the presence or absence of various enhancers. The skin fluxes of model compounds were calculated based on the data obtained using the method engaged with the diffusion cell system. The statistical design of experiments (DoE) based on the factorial approach was used to find variables that have a significant impact on the outcomes. For the prediction of skin flux, a quantitative equation was derived using the data-mining approach on the relationship between skin permeation of model compounds (~125 mg/ml) and involved physicochemical variables. The most influential variables for the skin flux of propionic acid derivatives were the melting point (0.97) followed by the presence of enantiomer (0.95), molecular mass (0.93), log P values (0.86), and aqueous solubility (0.80). It was concluded that the skin flux of molecular compounds can be predicted based on the relationship between their physicochemical properties and the interaction with cofactors including additives and enhancers in the vehicles.


Asunto(s)
Minería de Datos/métodos , Propionatos/administración & dosificación , Propionatos/farmacocinética , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiología , Administración Cutánea , Animales , Fenómenos Químicos , Ratones , Ratones Pelados , Técnicas de Cultivo de Órganos/métodos , Propionatos/química , Piel/efectos de los fármacos , Piel/metabolismo , Solubilidad
9.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-33669452

RESUMEN

Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-ß-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), applied topically protects against the ultraviolet radiation (UV) induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and the suppression of contact hypersensitivity (CHS) in female mice. Here, we compare these responses in female versus male Skh:hr1 mice, in ER-ß-/-/-- versus wild-type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. The induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice than in male Skh:hr1 or ER-ß-/- mice, respectively. This correlated with the reduced sunburn inflammation due to 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-ß-/- mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-ß-/-, or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory, and immune photoprotection by 1,25(OH)2D favoring female mice that is dependent on the presence of ER-ß.


Asunto(s)
Calcitriol/administración & dosificación , Receptor beta de Estrógeno/metabolismo , Transducción de Señal/efectos de la radiación , Quemadura Solar/tratamiento farmacológico , Quemadura Solar/metabolismo , Protectores Solares/administración & dosificación , Rayos Ultravioleta , Administración Cutánea , Animales , Dermatitis por Contacto/tratamiento farmacológico , Modelos Animales de Enfermedad , Receptor beta de Estrógeno/genética , Femenino , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/efectos de la radiación , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Dímeros de Pirimidina/metabolismo , Dímeros de Pirimidina/efectos de la radiación , Factores Sexuales , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Neoplasias Cutáneas/prevención & control , Quemadura Solar/prevención & control
10.
Nat Commun ; 12(1): 1827, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33758187

RESUMEN

Hereditary cystatin C amyloid angiopathy is a dominantly inherited disease caused by a leucine to glutamine variant of human cystatin C (hCC). L68Q-hCC forms amyloid deposits in brain arteries associated with micro-infarcts, leading ultimately to paralysis, dementia and death in young adults. To evaluate the ability of molecules to interfere with aggregation of hCC while informing about cellular toxicity, we generated cells that produce and secrete WT and L68Q-hCC and have detected high-molecular weight complexes formed from the mutant protein. Incubations of either lysate or supernatant containing L68Q-hCC with reducing agents glutathione or N-acetyl-cysteine (NAC) breaks oligomers into monomers. Six L68Q-hCC carriers taking NAC had skin biopsies obtained to determine if hCC deposits were reduced following NAC treatment. Remarkably, ~50-90% reduction of L68Q-hCC staining was observed in five of the treated carriers suggesting that L68Q-hCC is a clinical target for reducing agents.


Asunto(s)
Acetilcisteína/farmacología , Proteínas Amiloidogénicas/metabolismo , Angiopatía Amiloide Cerebral Familiar/dietoterapia , Cistatina C/metabolismo , Cistatinas/metabolismo , Acetilcisteína/administración & dosificación , Acetilcisteína/análogos & derivados , Acetilcisteína/química , Proteínas Amiloidogénicas/química , Proteínas Amiloidogénicas/genética , Biopsia , Angiopatía Amiloide Cerebral Familiar/tratamiento farmacológico , Angiopatía Amiloide Cerebral Familiar/genética , Cistatina C/química , Cistatina C/genética , Cistatinas/química , Cistatinas/genética , Expresión Génica , Glutatión/química , Glutatión/farmacología , Células HEK293 , Humanos , Piel/efectos de los fármacos , Piel/metabolismo , Adulto Joven
11.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652742

RESUMEN

Impressic acid (IPA), a lupane-type triterpenoid from Acanthopanax koreanum, has many pharmacological activities, including the attenuation of vascular endothelium dysfunction, cartilage destruction, and inflammatory diseases, but its influence on atopic dermatitis (AD)-like skin lesions is unknown. Therefore, we investigated the suppressive effect of IPA on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin symptoms in mice and the underlying mechanisms in cells. IPA attenuated the DNCB-induced increase in the serum concentrations of IgE and thymic stromal lymphopoietin (TSLP), and in the mRNA levels of thymus and activation regulated chemokine(TARC), macrophage derived chemokine (MDC), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice. Histopathological analysis showed that IPA reduced the epidermal/dermal thickness and inflammatory and mast cell infiltration of ear tissue. In addition, IPA attenuated the phosphorylation of NF-κB and IκBα, and the degradation of IκBα in ear lesions. Furthermore, IPA treatment suppressed TNF-α/IFN-γ-induced TARC expression by inhibiting the NF-κB activation in cells. Phosphorylation of extracellular signalregulated protein kinase (ERK1/2) and the signal transducer and activator of transcription 1 (STAT1), the upstream signaling proteins, was reduced by IPA treatment in HaCaT cells. In conclusion, IPA ameliorated AD-like skin symptoms by regulating cytokine and chemokine production and so has therapeutic potential for AD-like skin lesions.


Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/metabolismo , Factor de Transcripción STAT1/metabolismo , Triterpenos/uso terapéutico , Animales , Línea Celular , Citocinas/metabolismo , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología
12.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652999

RESUMEN

Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as Astragalus membranaceus BUNGE, Schizonepeta tenuifolia Briq., Cryptotympana pustulata Fabr., Angelica sinensis Diels, Arctium lappa L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.


Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Piel/efectos de los fármacos , Animales , Dermatitis Atópica/patología , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Plantas Medicinales/química , Piel/patología
13.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33672928

RESUMEN

Extensive water loss and melanin hyperproduction can cause various skin disorders. Low-temperature argon plasma (LTAP) has shown the possibility of being used for the treatment of various skin diseases, such as atopic dermatitis and skin cancer. However, the role of LTAP in regulating skin moisturizing and melanogenesis has not been investigated. In this study, we aimed to determine the effect of LTAP on yes-associated protein (YAP), a major transcriptional coactivator in the Hippo signaling pathway that is involved in skin moisturizing and melanogenesis-regulating markers. In normal human epidermal keratinocytes (NHEKs), the human epidermal keratinocyte line HaCaT, and human dermal fibroblasts (HDFs), we found that LTAP exhibited increased expression levels of YAP protein. In addition, the expression levels of filaggrin (FLG), which is involved in natural moisturizing factors (NMFs), and hyaluronic acid synthase (HAS), transglutaminase (TGM), and involucrin (IVL), which regulate skin barrier and moisturizing, were also increased after exposure to LTAP. Furthermore, collagen type I alpha 1 and type III alpha 1 (COL1A1, COL3A1) were increased after LTAP exposure, but the expression level of matrix metalloproteinase-3 (MMP-3) was reduced. Moreover, LTAP was found to suppress alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in murine melanoma B16F10 cells and normal human melanocytes (NHEMs). LTAP regulates melanogenesis of the melanocytes through decreased YAP pathway activation in a melanocortin 1 receptor (MC1R)-dependent manner. Taken together, our data show that LTAP regulates skin moisturizing and melanogenesis through modulation of the YAP pathway, and the effect of LTAP on the expression level of YAP varies from cell to cell. Thus, LTAP might be developed as a treatment method to improve the skin barrier, moisture content, and wrinkle formation, and to reduce melanin generation.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Argón/farmacología , Melaninas/metabolismo , Gases em Plasma/farmacología , Piel/efectos de los fármacos , Factores de Transcripción/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Células Cultivadas , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Melanocitos/citología , Melanocitos/efectos de los fármacos , Melanocitos/metabolismo , Ratones , Receptor de Melanocortina Tipo 1/metabolismo , Piel/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Temperatura , alfa-MSH/metabolismo
14.
Molecules ; 26(4)2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33672187

RESUMEN

Sunlight has a long list of positive effects on living beings [...].


Asunto(s)
Productos Biológicos/farmacología , Protectores contra Radiación/farmacología , Piel/efectos de los fármacos , Humanos , Piel/metabolismo
15.
Molecules ; 26(4)2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33672029

RESUMEN

Exposure to reactive oxygen species can easily result in serious diseases, such as hyperproliferative skin disorders or skin cancer. Herbal extracts are widely used as antioxidant sources in different compositions. The importance of antioxidant therapy in inflammatory conditions has increased. Innovative formulations can be used to improve the effects of these phytopharmacons. The bioactive compounds of Plantago lanceolata (PL) possess different effects, such as anti-inflammatory, antioxidant, and bactericidal pharmacological effects. The objective of this study was to formulate novel liquid crystal (LC) compositions to protect Plantago lanceolata extract from hydrolysis and to improve its effect. Since safety is an important aspect of pharmaceutical formulations, the biological properties of applied excipients and blends were evaluated using assorted in vitro methods on HaCaT cells. According to the antecedent toxicity screening evaluation, three surfactants were selected (Gelucire 44/14, Labrasol, and Lauroglycol 90) for the formulation. The dissolution rate of PL from the PL-LC systems was evaluated using a Franz diffusion chamber apparatus. The antioxidant properties of the PL-LC systems were evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA) assessments. Our results suggest that these compositions use a nontraditional, rapid-permeation pathway for the delivery of drugs, as the applied penetration enhancers reversibly alter the barrier properties of the outer stratum corneum. These excipients can be safe and highly tolerable thus, they could improve the patient's experience and promote adherence.


Asunto(s)
Composición de Medicamentos , Cristales Líquidos/química , Extractos Vegetales/farmacología , Plantago/química , Piel/efectos de los fármacos , Compuestos de Bifenilo/química , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Impedancia Eléctrica , Depuradores de Radicales Libres/farmacología , Humanos , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Malondialdehído/metabolismo , Permeabilidad , Picratos/química , Piel/efectos de la radiación , Rayos Ultravioleta
16.
Carbohydr Polym ; 260: 117767, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33712125

RESUMEN

Wound healing is a dynamic and intricate process, and newly dressings are urgently needed to promote wound healing over the multiple stages. Herein, two water-soluble adenine-modified chitosan (CS-A) derivatives were synthesized in aqueous solutions and freeze-dried to obtain porous sponge-like dressings. The novel derivatives displayed antibacterial activities against S. aureus and E. coli. Moreover, CS-A derivatives demonstrated excellent hemocompatibility and cytocompatibility, as well as promoted the proliferation of the wound cells by shortening the G1 phase and improving DNA duplication efficiency. The ability of CS-A sponges to promote wound healing was studied in a full-thickness skin defect model. The histological analysis and immunohistochemical staining showed that the wounds treated with CS-A sponges displayed fewer inflammatory cells, and faster regeneration of epithelial tissue, collagen deposition and neovascularization. Therefore, CS-A derivatives have potential application in wound dressings and provide new ideas for the design of multifunctional biomaterials.


Asunto(s)
Adenina/química , Materiales Biocompatibles/química , Quitosano/química , Animales , Vendajes , Materiales Biocompatibles/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Liofilización , Masculino , Ratones , Porosidad , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Piel/patología , Cicatrización de Heridas/efectos de los fármacos
17.
Carbohydr Polym ; 260: 117777, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33712133

RESUMEN

The combination of alginate, hyaluronic acid and multivalent ions have been reported to form alginate-hyaluronic acid ionic-crosslinking hydrogels for biomedical applications. However, injectable alginate-hyaluronic acid ionic-crosslinking hydrogels with satisfactory shear-thinning property have rarely been reported. In this study, we successfully developed an ionic-crosslinked alginate-hyaluronic acid hydrogel by simple assembly of alginate-hyaluronic acid mixture and Fe3+ complex. This hydrogel could fully recover within seconds after damaged, while displayed shear thinning behavior and good injectability which were contributed by the reversible and dynamic metal-ligand interactions formed via ferric ions and carboxyl groups of the polymers. Moreover, the local degradation of this hydrogel giving the hydrogel sustained ferric ions release property, of which led to potential long-term antibacterial activities against multiple types of bacteria including gram-negative Escherichia coli and gram-positive Staphylococcus aureus, as well as representative oral pathogenic bacteria Streptococcus mutans and Porphyromonas gingivalis.


Asunto(s)
Alginatos/química , Antiinfecciosos/química , Compuestos Férricos/química , Ácido Hialurónico/química , Hidrogeles/química , Animales , Antiinfecciosos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Femenino , Compuestos Férricos/metabolismo , Humanos , Hidrogeles/farmacología , Ratones , Ratones Endogámicos BALB C , Porphyromonas/efectos de los fármacos , Reología , Piel/efectos de los fármacos , Piel/patología , Staphylococcus aureus/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos
18.
Carbohydr Polym ; 261: 117870, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33766357

RESUMEN

Effective wound dressings are of great significance in preventing infections and promoting wound healing. However, most existing hydrogel dressings have an inadequacy in either mechanical performance, biological activities, or versatilities. Here we presented a double-network cross-linked polysaccharide-based hydrogel composed of collagen peptide-functionalized carboxymethyl chitosan (CS) and oxidized methacrylate sodium alginate (SA). The hydrogel possessed interconnected porous morphologies, suitable swelling ratios, excellent mechanical properties, and favorable biocompatibility. Meanwhile, the in vivo studies using a mouse full-thickness skin defect model showed that the double-network CS/SA hydrogel significantly accelerated wound healing by regulating the inflammatory process, promoting collagen deposition, and improving vascularization. Therefore, the functionalized double-network hydrogel should be a potential candidate as wound dressings.


Asunto(s)
Vendas Hidrocoloidales , Hidrogeles , Polisacáridos/química , Cicatrización de Heridas/efectos de los fármacos , Alginatos/síntesis química , Alginatos/química , Alginatos/uso terapéutico , Animales , Células Cultivadas , Quitosano/análogos & derivados , Quitosano/síntesis química , Quitosano/química , Quitosano/uso terapéutico , Colágeno/síntesis química , Colágeno/química , Colágeno/farmacocinética , Colágeno/uso terapéutico , Humanos , Hidrogeles/síntesis química , Hidrogeles/química , Hidrogeles/uso terapéutico , Ensayo de Materiales , Ratones , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/química , Fragmentos de Péptidos/farmacocinética , Fragmentos de Péptidos/uso terapéutico , Polisacáridos/uso terapéutico , Piel/efectos de los fármacos , Piel/lesiones , Piel/patología
19.
Int J Nanomedicine ; 16: 1457-1472, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33654396

RESUMEN

Purpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity. Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model. Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity. Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.


Asunto(s)
Diflunisal/administración & dosificación , Sistemas de Liberación de Medicamentos , Emulsiones/química , Nanogeles/química , Polietilenglicoles/química , Polietileneimina/química , Administración Tópica , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Carragenina , Diflunisal/química , Diflunisal/farmacología , Diflunisal/uso terapéutico , Modelos Animales de Enfermedad , Composición de Medicamentos , Liberación de Fármacos , Edema/tratamiento farmacológico , Edema/patología , Conductividad Eléctrica , Concentración de Iones de Hidrógeno , Masculino , Tamaño de la Partícula , Permeabilidad , Transición de Fase , Ratas , Piel/efectos de los fármacos , Absorción Cutánea/efectos de los fármacos , Solubilidad , Tensoactivos/química , Viscosidad
20.
AAPS PharmSciTech ; 22(3): 104, 2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33718986

RESUMEN

Pain is a phenomenon present in the majority of the population, affecting, among others, the elderly, overweight people, and especially recently operated patients, analgesia being necessary. In the specific case of relief of postoperative pain, different kinds of anesthetics are being used, among them bupivacaine, a widely used drug which promotes long-lasting analgesic effects. However, cardiotoxicity and neurotoxicity are related to its repetitive use. To overcome these shortcomings, Novabupi® (a racemic mixture) was developed and is marketed as an injectable solution. This formulation contains an enantiomeric excess of the levogyre isomer, which has reduced toxicity effects. Seeking to rationalize its use by extending the duration of effect and reducing the number of applications, the objectives of this work were to develop and evaluate liposomes containing Novabupi (LBPV), followed by incorporation into thermogel. Liposomes were prepared using the lipid hydration method, followed by size reduction using sonication, and the developed formulations were characterized by hydrodynamic diameter, polydispersity index (PDI), surface zeta potential, and encapsulation efficiency. The selected optimal liposomal formulation was successfully incorporated into a thermogel without loss of thermoresponsive properties, being suitable for administration as a subcutaneous injection. In the ex vivo permeation studies with fresh rodent skin, the thermogel with liposomes loaded with 0.5% LBPV (T-gel formulation 3) showed higher permeation rates compared to the starting formulation, thermogel with 0.5% LBPV (T-Gel 1), which will probably translate into better therapeutic benefits for treatment of postoperative analgesia, especially with regard to the number of doses applied.


Asunto(s)
Analgesia/métodos , Levobupivacaína/administración & dosificación , Levobupivacaína/farmacocinética , Dolor/tratamiento farmacológico , Dolor/metabolismo , Animales , Bovinos , Pollos , Membrana Corioalantoides/efectos de los fármacos , Membrana Corioalantoides/metabolismo , Geles , Humanos , Liposomas , Masculino , Ratones , Células 3T3 NIH , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Piel/efectos de los fármacos , Piel/metabolismo , Absorción Cutánea/efectos de los fármacos , Absorción Cutánea/fisiología
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