RESUMEN
The hair follicle is the basis of hair regeneration, and the dermal papilla is one of the most important structures in hair regeneration. New intervention and reversal strategies for hair loss may arise due to the prevention of oxidative stress. GC/MS analysis was used to determine the compounds contained in NSO. Then, NSO was applied to DPC for cell proliferation and oxidative stress experiments. RNA-seq was performed in cells treated with NSO and minoxidil. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify the gene expression. The effects of NSO on hair length, weight, the number and depth of hair follicles, and the dermal thickness were also studied. GC/MS analysis showed that the main components of NSO were eicosapentaenoic acid, palmitic acid, and linoleic acid. NSO promotes DPC proliferation and reduces H2O2-mediated oxidative damage. NSO can also activate hair growth-related pathways and upregulate antioxidant-related genes analyzed by gene profiling. The topical application of NSO significantly promotes hair growth and increases hair length and weight in mice. NSO extract promotes hair growth and effectively inhibits oxidative stress, which is beneficial for the prevention and treatment of hair loss.
Asunto(s)
Proliferación Celular , Folículo Piloso , Cabello , Estrés Oxidativo , Proliferación Celular/efectos de los fármacos , Animales , Humanos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Folículo Piloso/citología , Ratones , Estrés Oxidativo/efectos de los fármacos , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Antioxidantes/farmacología , Dermis/metabolismo , Dermis/citología , Dermis/efectos de los fármacosRESUMEN
Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.
Asunto(s)
Folículo Piloso , Hidroxiprostaglandina Deshidrogenasas , Humanos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Hidroxiprostaglandina Deshidrogenasas/metabolismo , Hidroxiprostaglandina Deshidrogenasas/antagonistas & inhibidores , Dihidrotestosterona/farmacología , Dihidrotestosterona/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Dermis/metabolismo , Dermis/citología , Dermis/efectos de los fármacos , Células Cultivadas , Vía de Señalización Wnt/efectos de los fármacos , Alopecia/tratamiento farmacológico , Alopecia/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Inhibidores Enzimáticos/farmacologíaRESUMEN
Due to the limitations of the current skin wound treatments, it is highly valuable to have a wound healing formulation that mimics the extracellular matrix (ECM) and mechanical properties of natural skin tissue. Here, a novel biomimetic hydrogel formulation has been developed based on a mixture of Agarose-Collagen Type I (AC) combined with skin ECM-related components: Dermatan sulfate (DS), Hyaluronic acid (HA), and Elastin (EL) for its application in skin tissue engineering (TE). Different formulations were designed by combining AC hydrogels with DS, HA, and EL. Cell viability, hemocompatibility, physicochemical, mechanical, and wound healing properties were investigated. Finally, a bilayered hydrogel loaded with fibroblasts and mesenchymal stromal cells was developed using the Ag-Col I-DS-HA-EL (ACDHE) formulation. The ACDHE hydrogel displayed the best in vitro results and acceptable physicochemical properties. Also, it behaved mechanically close to human native skin and exhibited good cytocompatibility. Environmental scanning electron microscopy (ESEM) analysis revealed a porous microstructure that allows the maintenance of cell growth and ECM-like structure production. These findings demonstrate the potential of the ACDHE hydrogel formulation for applications such as an injectable hydrogel or a bioink to create cell-laden structures for skin TE.
Asunto(s)
Materiales Biomiméticos , Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ingeniería de Tejidos/métodos , Supervivencia Celular/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Cicatrización de Heridas/efectos de los fármacos , Colágeno Tipo I/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Dermatán Sulfato/química , Dermatán Sulfato/farmacología , Fibroblastos/efectos de los fármacos , Elastina/química , Matriz Extracelular/metabolismo , Biomimética/métodos , Sefarosa/química , Dermis/efectos de los fármacos , Dermis/metabolismo , Dermis/citología , AnimalesRESUMEN
Despite the remarkable advances of dermal fillers that reduce wrinkles caused by dermis thickness reduction, they still lack effective hydrogel systems that stimulate collagen generation along with injection convenience. Here, we develop a stem cell-derived extracellular vesicle (EV)-bearing thermosensitive hydrogel (EVTS-Gel) for effective in vivo collagen generation. The TS-Gel undergoes sol-gel transition at 32.6 °C, as demonstrated by the storage and loss moduli crossover. Moreover, the TS-Gel and the EVTS-Gel have comparable rheological properties. Both hydrogels are injected in a sol state; hence, they require lower injection forces than conventional hydrogel-based dermal fillers. When locally administered to mouse skin, the TS-Gel extends the retention time of EVs by 2.23 times. Based on the nature of the controlled EV release, the EVTS-Gel significantly inhibits the dermis thickness reduction caused by aging compared to the bare EV treatment for 24 weeks. After a single treatment, the collagen layer thickness of the EVTS-Gel-treated dermis becomes 2.64-fold thicker than that of the bare EV-treated dermis. Notably, the collagen generation efficacy of the bare EV is poorer than that of the EVTS-Gel of a 10× lesser dose. Overall, the EVTS-Gel shows potential as an antiaging dermal filler for in vivo collagen generation.
Asunto(s)
Colágeno , Dermis , Vesículas Extracelulares , Hidrogeles , Animales , Ratones , Dermis/metabolismo , Dermis/efectos de los fármacos , Colágeno/química , Hidrogeles/química , Hidrogeles/farmacología , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Humanos , Células Madre/citología , Células Madre/metabolismo , Células Madre/efectos de los fármacos , Rellenos Dérmicos/química , Rellenos Dérmicos/farmacologíaRESUMEN
BACKGROUND/AIM: Dermal papilla (DP) stem cells are known for their remarkable regenerative capacity, making them a valuable model for assessing the effects of natural products on cellular processes, including stemness, and autophagy. MATERIALS AND METHODS: Autophagy and stemness characteristics were assessed using real-time RT-PCR to analyze mRNA levels, along with immunofluorescence and western blot techniques for protein level evaluation. RESULTS: Butterfly Pea, Emblica Fruits, Kaffir Lime, and Thunbergia Laurifolia extracts induced autophagy in DP cells. Kaffir Lime-treated cells exhibited increase in the OCT4, NANOG, and SOX2 mRNA (6-, 5, and 5.5-fold, respectively), and protein levels (4-, 3-, and 1.5-fold, respectively). All extracts activated the survival protein kinase B (Akt) in DP cells. CONCLUSION: Natural products are a promising source for promoting hair growth by rejuvenating hair stem cells.
Asunto(s)
Autofagia , Productos Biológicos , Folículo Piloso , Extractos Vegetales , Células Madre , Autofagia/efectos de los fármacos , Humanos , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Células Madre/citología , Productos Biológicos/farmacología , Extractos Vegetales/farmacología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/citología , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Proteína Homeótica Nanog/metabolismo , Proteína Homeótica Nanog/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXB1/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Diferenciación Celular/efectos de los fármacosRESUMEN
Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for its potential to promote hair regrowth. However, the precise mechanism by which Enz_MoriL affects human hair follicle dermal papilla cells (hDPCs) remains unclear. The aim of this study was to investigate the molecular basis of Enz_MoriL's effect on hair growth in hDPCs. Interferon-gamma (IFN-γ) was used to examine the effects of Enz_MoriL on hDPCs during the anagen and catagen phases, as well as under conditions mimicking alopecia areata (AA). Enz_MoriL demonstrated the ability to promote cell proliferation in both anagen and catagen stages. It increased the levels of active ß-catenin in the catagen stage induced by IFN-γ, leading to its nuclear translocation. This effect was achieved by increasing the phosphorylation of GSK3ß and decreasing the expression of DKK-1. This stimulation induced proliferation in hDPCs and upregulated the expression of the Wnt family members 3a, 5a, and 7a at the transcript level. Additionally, Enz_MoriL suppressed JAK1 and STAT3 phosphorylation, contrasting with IFN-γ, which induced them in the catagen stage. In conclusion, Enz_MoriL directly induced signals for anagen re-entry into hDPCs by affecting the Wnt/ß-catenin pathway and enhancing the production of growth factors. Furthermore, Enz_MoriL attenuated and reversed the interferon-induced AA-like environment by blocking the JAK-STAT pathway in hDPCs.
Asunto(s)
Alopecia Areata , Proliferación Celular , Folículo Piloso , Interferón gamma , Vía de Señalización Wnt , beta Catenina , Humanos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/citología , Folículo Piloso/metabolismo , Proliferación Celular/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Interferón gamma/metabolismo , beta Catenina/metabolismo , Alopecia Areata/metabolismo , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/patología , Células Cultivadas , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Quinasas Janus/metabolismo , Dermis/citología , Dermis/efectos de los fármacos , Fosforilación/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Proteína Wnt-5a/metabolismo , Janus Quinasa 1/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Transcripción STAT/metabolismoRESUMEN
Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.
Asunto(s)
Autofagia , Cabello , Animales , Ratones , Humanos , Autofagia/efectos de los fármacos , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/citología , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Dermis/citología , Dermis/efectos de los fármacos , Canales de Potencial de Receptor Transitorio/metabolismo , Señalización del Calcio/efectos de los fármacosRESUMEN
Dermal papilla cell (DPC) belongs to a specialized mesenchymal stem cell for hair follicle regeneration. Maintaining the ability of DPCs to stimulate hair in vitro culture is important for hair follicle morphogenesis and regeneration. As the third generation of platelet concentrate, injectable platelet-rich fibrin (i-PRF) is a novel biomaterial containing many growth factors and showing promising effects on tissue reconstruction. We aimed to explore the influences of i-PRF on the proliferative, migratory, as well as trichogenic ability of DPCs and compared the effects of i-PRF and platelet-rich plasma (PRP), the first generation of platelet concentrate. Both PRP and i-PRF facilitated DPCs proliferation, and migration, along with trichogenic inductivity as well as stimulated the TGF-ß/Smad pathway, while the impacts of i-PRF were more significant than PRP. A small molecule inhibitor of TGF-beta receptor I, Galunisertib, was also applied to treat DPCs, and it rescued the impacts of i-PRF on the proliferative, migratory, trichogenic inductivity, and proteins-associated with TGF-ß/Smad pathway in DPCs. These findings revealed that i-PRF had better effects than PRP in enhancing the proliferative, migratory, and hair-inducing abilities of DPCs by the TGF-ß/Smad pathway, which indicated the beneficial role of i-PRF in hair follicle regeneration.
Asunto(s)
Movimiento Celular , Proliferación Celular , Folículo Piloso , Fibrina Rica en Plaquetas , Transducción de Señal , Proteínas Smad , Factor de Crecimiento Transformador beta , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/citología , Proteínas Smad/metabolismo , Humanos , Fibrina Rica en Plaquetas/metabolismo , Movimiento Celular/efectos de los fármacos , Dermis/citología , Dermis/metabolismo , Dermis/efectos de los fármacos , Células Cultivadas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Plasma Rico en Plaquetas/metabolismo , InyeccionesRESUMEN
Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of ß-Catenin. Since several anagen-inductive genes are regulated by ß-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated ß-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3ß/ß-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H2O2)-induced HDPCs. The senescence-associated ß-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H2O2-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.
Asunto(s)
Glucógeno Sintasa Quinasa 3 beta , Peróxido de Hidrógeno , Estrés Oxidativo , Floroglucinol , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , beta Catenina , Humanos , Floroglucinol/farmacología , Floroglucinol/análogos & derivados , Estrés Oxidativo/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Transducción de Señal/efectos de los fármacos , beta Catenina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Fosforilación/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/citología , Dermis/citología , Dermis/metabolismo , Dermis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Alopecia/tratamiento farmacológico , Alopecia/metabolismoRESUMEN
Ultraviolet (UV)-induced skin photoaging is caused by qualitative and quantitative degradation of dermal extracellular matrix components such as collagen and elastic fibers. Elastic fibers are important for maintaining cutaneous elasticity, despite their small amount in the skin. Previously, microfibril-associated protein 4 (MFAP-4), which is downregulated in photoaging dermis, has been found to be essential for elastic fiber formation by interaction with both fibrillin-1 and elastin, which are core components of elastic fiber. In addition, enhanced cutaneous MFAP-4 expression in a human skin-xenografted murine photoaging model protects against UV-induced photodamage accompanied by the prevention of elastic fiber degradation and aggravated elasticity. We therefore hypothesized that the upregulation of MFAP-4 in dermal fibroblasts may more efficiently accelerate elastic fiber formation. We screened botanical extracts for MFAP-4 expression-promoting activity in normal human dermal fibroblasts (NHDFs). We found that rosemary extract markedly promotes early microfibril formation and mature elastic fiber formation along with a significant upregulation of not only MFAP-4 but also fibrillin-1 and elastin in NHDFs. Furthermore, rosmarinic acid, which is abundant in rosemary extract, accelerated elastic fiber formation via upregulation of transforming growth factor ß-1. This was achieved by the induction of cAMP response element-binding protein phosphorylation, demonstrating that rosmarinic acid represents one of the active ingredients in rosemary extract. Based on the findings in this study, we conclude that rosemary extract and rosmarinic acid represent promising materials that exert a preventive or ameliorative effect on skin photoaging by accelerating elastic fiber formation.
Asunto(s)
Cinamatos , Depsidos , Tejido Elástico , Elastina , Fibrilina-1 , Fibroblastos , Extractos Vegetales , Ácido Rosmarínico , Envejecimiento de la Piel , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Depsidos/farmacología , Fibrilina-1/metabolismo , Cinamatos/farmacología , Extractos Vegetales/farmacología , Elastina/metabolismo , Tejido Elástico/efectos de los fármacos , Tejido Elástico/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Células Cultivadas , Rosmarinus/química , Regulación hacia Arriba/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/citología , Piel/patología , Piel/metabolismo , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Rayos Ultravioleta/efectos adversos , Proteínas de la Matriz Extracelular/metabolismo , AdipoquinasRESUMEN
Over several decades, excess glucocorticoids (GCs) of endogenous or exogenous origin have been recognized to significantly inhibit collagen synthesis and accelerate skin aging. However, little is known regarding their molecular mechanisms. We hypothesized that the action of GCs on collagen production is at least partially through the glucocorticoid receptor (GR) and its target genes, and therefore aimed to identify GR target genes that potentially inhibit collagen synthesis in Hs68 human dermal fibroblasts. We first confirmed that dexamethasone, a synthetic GC, induced canonical GR signaling in dermal fibroblasts. We then collected 108 candidates for GR target genes reported in previous studies on GR target genes and verified that 17 genes were transcriptionally upregulated in dexamethasone-treated dermal fibroblasts. Subsequently, by individual knockdown of the 17 genes, we identified that six genes, AT-rich interaction domain 5B, FK506 binding protein 5, lysyl oxidase, methylenetetrahydrofolate dehydrogenase (NADP + dependent) 2, zinc finger protein 36, and zinc fingers and homeoboxes 3, are potentially involved in GC-mediated inhibition of collagen synthesis. The present study sheds light on the molecular mechanisms of GC-mediated skin aging and provides a basis for further research on the biological characteristics of individual GR target genes.
Asunto(s)
Colágeno , Dermis , Fibroblastos , Glucocorticoides , Receptores de Glucocorticoides , Humanos , Colágeno/biosíntesis , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Dexametasona/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glucocorticoides/farmacología , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismoRESUMEN
BACKGROUND: Topical skin care products often do not reach the deeper layers of the skin, and oral hydrolyzed collagen is one of the newest and most popular systemic supplementations for skin rejuvenation. However, there are limited information in case of Middle Eastern consumers OBJECTIVE: The purpose of this study was to evaluate the tolerability and efficacy of an oral collagen supplement for improvement of skin elasticity, hydration, and roughness in Middle Eastern consumers. METHODS AND MATERIALS: It was a 12-week, before-after clinical study, conducted on 20 participants (18 women and 2 men) aged 44.15 ± 5.36 years with skin type III-IV. Skin elasticity parameters (R0, R2, R5, and R7), skin hydration and friction, as well as the thickness and echo density of the dermis, were measured after six and 12 weeks daily intake of the study product, as well as 4 weeks after stopping its use (week 16). Participants' satisfaction was assessed on the basis of their answers to the standard questionnaire, and tolerability of the product was assessed by monitoring the adverse effects. RESULTS: A significant improvement was detected in R2, R5, and skin friction at week 12 (p-values 0.041, 0.012 and <0.01, respectively). At week 16, the values remained at an increased level, which indicates the persistence of the results. The increase of dermis density in week 16 was also significant (p-value = 0.03). Moderate overall satisfaction was reported with the treatment, and a few gastrointestinal complications were reported. CONCLUSION: The study demonstrated that oral collagen peptides could significantly improve the skin elasticity, roughness, and dermis echo density, and they also proved to be safe and well-tolerated.
Asunto(s)
Colágeno , Piel , Humanos , Masculino , Femenino , Colágeno/administración & dosificación , Colágeno/efectos adversos , Administración Oral , Suplementos Dietéticos/efectos adversos , Piel/efectos de los fármacos , Adulto , Persona de Mediana Edad , Pueblos de Medio Oriente , Envejecimiento de la Piel , Dermis/efectos de los fármacos , Irán , Satisfacción PersonalRESUMEN
Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer and widespread use, paclitaxel also damages healthy tissues, including the skin. However, the mechanisms that drive these skin adverse events are not clearly understood. In the present study, we demonstrated, by using both primary epidermal keratinocytes (NHEK) and a 3D epidermis model, that paclitaxel impairs different cellular processes: paclitaxel increased the release of IL-1α, IL-6, and IL-8 inflammatory cytokines, produced reactive oxygen species (ROS) release and apoptosis, and reduced the endothelial tube formation in the dermal microvascular endothelial cells (HDMEC). Some of the mechanisms driving these adverse skin events in vitro are mediated by the activation of toll-like receptor 4 (TLR-4), which phosphorylate transcription of nuclear factor kappa B (NF-κb). This is the first study analyzing paclitaxel effects on healthy human epidermal cells with an epidermis 3D model, and will help in understanding paclitaxel's effects on the skin.
Asunto(s)
Citocinas/metabolismo , Epidermis/metabolismo , Queratinocitos/citología , Paclitaxel/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Receptor Toll-Like 4/metabolismo , Animales , Células 3T3 BALB , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Epidermis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-1alfa/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , FN-kappa B/metabolismo , Paclitaxel/farmacología , Fosforilación/efectos de los fármacosRESUMEN
Dermal papilla cells (DPCs) are a source of nutrients and growth factors, which support the proliferation and growth of keratinocytes as well as promoting the induction of new hair follicles and maintenance of hair growth. The protection from reactive oxygen species (ROS) and the promotion of angiogenesis are considered two of the basal mechanisms to preserve the growth of the hair follicle. In this study, a noncrosslinked hyaluronic acid (HA) filler (HYDRO DELUXE BIO, Matex Lab S.p.A.) containing several amino acids was tested with in vitro assays on human follicle dermal papilla cells (HFDPCs). The experiments were carried out to investigate the possible protection against oxidative stress and the ability to increase the vascular endothelial growth factor (VEGF) release. The results demonstrated the restoration of cell viability against UVB-induced cytotoxicity and an increase in the VEGF secretion. These data demonstrate the capability of the product to modulate human dermal papilla cells, suggesting a future use in mesotherapy, a minimally invasive local intradermal therapy (LIT), after further clinical investigations.
Asunto(s)
Dermis/metabolismo , Folículo Piloso/metabolismo , Ácido Hialurónico/farmacología , Células Cultivadas , Dermis/efectos de los fármacos , Dermis/crecimiento & desarrollo , Cabello/crecimiento & desarrollo , Folículo Piloso/efectos de los fármacos , Humanos , Ácido Hialurónico/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Hair follicle regeneration has been successful in mice but failed in human being for years. Dermal papilla cells, a specialized mesenchymal stem cell derived from dermal papilla within hair follicles, is considered the key cells for hair follicle regeneration function as both regeneration initiator and regulator. Injectable platelet rich fibrin (i-PRF), a novel biomaterial rich in a variety of growth factors and three-dimensional scaffolds, has shown promising effects on tissue regeneration. In this study, we aimed to evaluate the application of i-PRF in human hair follicle regeneration by examining the biological effects of i-PRF on human dermal papilla cells (hDPCs). Biomaterial compatibility, cell viability, proliferation, migration, alkaline phosphatase activity and trichogenic inductivity were assessed after exposing hDPCs to different concentrations of i-PRF extracts. In addition, we investigated the ultrastructure of i-PRF with all cell components filtered. The results revealed that i-PRF possessing excellent biocompatibility and could significantly promote hDPCs proliferation, migration, and trichogenic inductivity. Furthermore, the concentration of i-PRF is able to remarkably influence hDPCs behavior in a dose-dependent pattern. Different concentrations exhibited differential effects on hDPCs behavior. In general, lower concentration promotes cell proliferation better than higher concentration, while higher concentration promotes cell function better reversely. Best concentration for hDPCs in vitro expending is 1% concentration. 20% concentration is optimal for hair follicle regeneration. In summary, our findings concluded that i-PRF facilitates hair follicle regeneration by promoting human dermal papilla cell proliferation, migration, and trichogenic inductivity.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dermis/efectos de los fármacos , Folículo Piloso/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Fibrina Rica en Plaquetas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Dermis/metabolismo , Femenino , Folículo Piloso/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Regarding that the chronic use of commonly available non-steroidal and anti-inflammatory drugs (NSAIDs) is often restricted by their adverse effects, there is still a current need to search for and develop new, safe and effective anti-inflammatory agents. As a continuation of our previous work, we designed and synthesized a series of 18 novel N-substituted-1,2,4-triazole-based derivatives of pyrrolo[3,4-d]pyridazinone 4a-c-9a-c. The target compounds were afforded via a convenient way of synthesis, with good yields. The executed cell viability assay revealed that molecules 4a-7a, 9a, 4b-7b, 4c-7c do not exert a cytotoxic effect and were qualified for further investigations. According to the performed in vitro test, compounds 4a-7a, 9a, 4b, 7b, 4c show significant cyclooxygenase-2 (COX-2) inhibitory activity and a promising COX-2/COX-1 selectivity ratio. These findings are supported by a molecular docking study which demonstrates that new derivatives take position in the active site of COX-2 very similar to Meloxicam. Moreover, in the carried out in vitro evaluation within cells, the title molecules increase the viability of cells pre-incubated with the pro-inflammatory lipopolysaccharide and reduce the level of reactive oxygen and nitrogen species (RONS) in induced oxidative stress. The spectroscopic and molecular modeling study discloses that new compounds bind favorably to site II(m) of bovine serum albumin. Finally, we have also performed some in silico pharmacokinetic and drug-likeness predictions. Taking all of the results into consideration, the molecules belonging to series a (4a-7a, 9a) show the most promising biological profile.
Asunto(s)
Antiinflamatorios/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Dermis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Piridazinas/química , Pirroles/química , Triazoles/química , Antiinflamatorios/química , Supervivencia Celular , Ciclooxigenasa 1/química , Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa/química , Dermis/citología , Dermis/enzimología , Diseño de Fármacos , Fibroblastos/citología , Fibroblastos/enzimología , Humanos , Técnicas In Vitro , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin-alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin-alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in Sus scrofa pigs. Keratin-alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin-alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin-alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration.
Asunto(s)
Alginatos/uso terapéutico , Quemaduras/terapia , Queratinas/uso terapéutico , Cicatrización de Heridas , Alginatos/química , Alginatos/farmacología , Animales , Vendas Hidrocoloidales , Quemaduras/patología , Quemaduras/fisiopatología , Células Cultivadas , Dermis/efectos de los fármacos , Dermis/patología , Dermis/fisiopatología , Humanos , Hidrogeles/química , Hidrogeles/uso terapéutico , Queratinas/química , Queratinas/farmacología , Masculino , Ensayo de Materiales , Índice de Severidad de la Enfermedad , Piel/efectos de los fármacos , Piel/patología , Piel/fisiopatología , Porcinos , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
Cordyline terminalis leaf extract (aqCT) possesses abundant polyphenols and other bioactive compounds, which are encapsulated in gelatin-polyethylene glycol-tyramine (GPT)/alpha-cyclodextrin (α-CD) gels to form the additional functional materials for biomedical applications. In this study, the gel compositions are optimized, and the GPT/α-CD ratios equal to or less than one half for solidification are found. The gelation time varies from 40.7 min to 5.0 h depending on the increase in GPT/α-CD ratios and aqCT amount. The aqCT extract disturbs the hydrogen bonding and host-guest inclusion of GPT/α-CD gel networks, postponing the gelation. Scanning electron microscope observation shows that all gels with or without aqCT possess a microarchitecture and porosity. GPT/α-CD/aqCT gels could release polyphenols from 110 to 350 nmol/mL at the first hour and sustainably from 5.5 to 20.2 nmol/mL for the following hours, which is controlled by feeding the aqCT amount and gel properties. GPT/α-CD/aqCT gels achieved significant antioxidant activity through a 100% scavenging DPPH radical. In addition, all gels are non-cytotoxic with a cell viability more than 85%. Especially, the GPT3.75α-CD10.5aqCT gels with aqCT amount of 3.1-12.5 mg/mL immensely enhanced the cell proliferation of GPT3.75α-CD10.5 gel without extract. These results suggest that the inherent bioactivities of aqCT endowed the resulting GPT/α-CD/aqCT gels with effective antioxidant and high biocompatibility, and natural polyphenols sustainably release a unique platform for a drug delivery system or other biomedical applications.
Asunto(s)
Cordyline/química , Dermis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Geles/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Polifenoles/farmacología , Células Cultivadas , Liberación de Fármacos , Geles/administración & dosificación , HumanosRESUMEN
New, tricyclic compounds containing a sulfonyl moiety in their structure, as potential safer COX inhibitors, were designed and synthesized. New derivatives have three conjugated rings and a sulfonyl group. A third ring, i.e., an oxazine, oxazepine or oxazocin, has been added to the 1,2-benzothiazine skeleton. Their anti-COX-1/COX-2 and cytotoxic effects in vitro on NHDF cells, together with the ability to interact with model membranes and the influence on reactive oxygen species and nitric oxide, were studied. Additionally, a molecular docking study was performed to understand the binding interaction of the compounds with the active site of cyclooxygenases. For the abovementioned biological evaluation of new tricyclic 1,2-benzothiazine derivatives, the following techniques and procedures were employed: the differential scanning calorimetry, the COX colorimetric inhibitor screening assay, the MTT, DCF-DA and Griess assays. All of the compounds studied demonstrated preferential inhibition of COX-2 compared to COX-1. Moreover, all the examined tricyclic 1,2-thiazine derivatives interacted with the phospholipid model membranes. Finally, they neither have cytotoxic potency, nor demonstrate significant influence on the level of reactive oxygen species or nitric oxide. Overall, the tricyclic 1,2-thiazine derivatives are good starting points for future pharmacological tests as a group of new anti-inflammatory agents.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Dermis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tiazinas/química , Antiinflamatorios no Esteroideos/química , Células Cultivadas , Inhibidores de la Ciclooxigenasa/química , Dermis/citología , Fibroblastos/citología , Humanos , Simulación del Acoplamiento Molecular , Prostaglandina-Endoperóxido Sintasas/químicaRESUMEN
BACKGROUND: Laminitis, an inflammation of the claw laminae, is one of the major causes of bovine lameness, which can lead to enormous economic losses and animal welfare problems in dairy farms. Angelica polysaccharide (AP) is proved to possess anti-inflammatory properties. But the role of AP on inflammatory response of the claw dermal cells has not been reported. The aim of this study was to investigate the anti-inflammatory effects of AP on lipopolysaccharide (LPS)-induced primary claw dermal cells of dairy cow and clarify the potential mechanisms. In the current research, the primary claw dermal cells were exposed to gradient concentrations of AP (10, 50, 100 µg/mL) in the presence of 10 µg/mL LPS. The levels of cytokines and nitric oxide (NO) were detected with ELISA and Griess colorimetric method. The mRNA expressions of TLR4, MyD88 and chemokines were measured with qPCR. The activation of NF-κB and MAPK signaling pathways was detected with western blotting. RESULTS: The results indicated that AP reduced the production of inflammatory mediators (TNF-α, IL-1ß, IL-6 and NO), downregulated the mRNA expression of TLR4, MyD88 and some pro-inflammatory chemokines (CCL2, CCL20, CXCL2, CXCL8, CXCL10), and suppressed the NF-κB and MAPK signaling pathways evidenced by inhibition of the phosphorylation of IκBα, p65 and ERK, JNK, p38. CONCLUSIONS: Our results demonstrated that AP may exert its anti-inflammatory effects on claw dermal cells of dairy cow by regulating the NF-κB and MAPK signaling pathways.