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1.
Exp Dermatol ; 31(11): 1699-1711, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35833307

RESUMEN

Interleukin (IL)-38 is a member of the IL-1 cytokine family with reported anti-inflammatory activity. The highest constitutive IL-38 expression is detected in the skin, where it is mainly produced by differentiating keratinocytes. However, little data are available regarding its biological functions. In this study, we investigated the role of IL-38 in skin physiology. We demonstrate here that dermal fibroblasts and epithelial cells of skin appendages, such as eccrine sweat glands and sebaceous glands, also express IL-38. Next, using two- and three-dimensional cell cultures, we show that endogenous expression of IL-38 correlates with keratinocyte differentiation and its ectopic overexpression inhibits keratinocyte proliferation and enhances differentiation. Accordingly, immunohistochemical analysis revealed downregulation of IL-38 in skin pathologies characterized by keratinocyte hyperproliferation, such as psoriasis and basal or squamous cell carcinoma. Finally, intracellular IL-38 can shuttle between the nucleus and the cytoplasm and its overexpression modulates the activity of the transcription regulators YAP and ID1. Our results indicate that IL-38 can act independently from immune system activation and suggest that it may affect the epidermis directly by decreasing proliferation and promoting differentiation of keratinocytes. These data suggest an important role of keratinocyte-derived IL-38 in skin homeostasis and pathologies characterized by epidermal alterations.


Asunto(s)
Queratinocitos , Psoriasis , Humanos , Queratinocitos/metabolismo , Epidermis/metabolismo , Piel/patología , Células Epidérmicas , Psoriasis/metabolismo , Diferenciación Celular , Proliferación Celular , Interleucinas/metabolismo
2.
Int J Mol Sci ; 23(23)2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36499664

RESUMEN

Mesenchymal stem cells have a known regenerative potential and are used in many indications. They secrete many growth factors, including for fibroblasts (FGF), endothelium (VEGF), as well as 14 anti-inflammatory cytokines, and they stimulate tissue regeneration, promoting the secretion of proteins and glycosaminoglycans of extracellular matrices, such as collagen I, II, III, and V, elastin, and also metalloproteinases. They secrete exosomes that contain proteins, nucleic acids, lipids, and enzymes. In addition, they show the activity of inactivating free radicals. The aim of this study was an attempt to collect the existing literature on the use of stem cells in the treatment of a burn wound. There were 81 studies included in the analysis. The studies differed in terms of the design, burn wound model, source of stem cells, and methods of cellular therapy application. No major side effects were reported, and cellular therapy reduced the healing time of the burn wound. Few case reports on human models did not report any serious adverse events. However, due to the heterogeneity of the evidence, cellular therapy in burn wound treatment remains an experimental method.


Asunto(s)
Quemaduras , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Cicatrización de Heridas , Quemaduras/terapia , Quemaduras/metabolismo , Tratamiento Basado en Trasplante de Células y Tejidos
3.
Int J Mol Sci ; 23(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36499763

RESUMEN

The microbiome's significance in chronic rhinosinusitis (CRS) is unclear. Antimicrobials are recommended in acute exacerbations of the disease (AECRS). Increasing rates of antibiotic resistance have stimulated research on alternative therapeutic options, including silver nanoparticles (AgNPs). However, there are concerns regarding the safety of silver administration. The aim of this study was to assess the biological activity of tannic acid-prepared AgNPs (TA-AgNPs) towards sinonasal pathogens and nasal epithelial cells (HNEpC). The minimal inhibitory concentration (MIC) for pathogens isolated from patients with AECRS was approximated using the well diffusion method. The cytotoxicity of TA-AgNPswas evaluated using an MTT assay and trypan blue exclusion. A total of 48 clinical isolates and 4 reference strains were included in the study (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiellaoxytoca, Acinetobacter baumannii, Serratia marcescens, Enterobacter cloacae). The results of the studies revealed that the MIC values differed between isolates, even within the same species. All the isolates were sensitive to TA-AgNPs in concentrations non-toxic to human cells during 24 h exposition. However, 48 h exposure to TA-AgNPs increased toxicity to HNEpC, narrowing their therapeutic window and enabling 19% of pathogens to resist the TA-AgNPs' biocidal action. It was concluded that TA-AgNPs are non-toxic for the investigated eukaryotic cells after short-term exposure and effective against most pathogens isolated from patients with AECRS, but sensitivity testing may be necessary before application.


Asunto(s)
Nanopartículas del Metal , Plata , Humanos , Plata/farmacología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Taninos/farmacología , Escherichia coli
4.
Biochim Biophys Acta Mol Cell Res ; 1864(2): 267-279, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27864076

RESUMEN

Bone marrow-derived cells are thought to participate and enhance the healing process contributing to skin cells or releasing regulatory cytokines. Directional cell migration in a weak direct current electric field (DC-EF), known as electrotaxis, may be a way of cell recruitment to the wound site. Here we examined the influence of electric field on bone marrow adherent cells (BMACs) and its potential role as a factor attracting mesenchymal stem cells to cutaneous wounds. We observed that in an external EF, BMAC movement was accelerated and highly directed with distinction of two cell populations migrating toward opposite poles: mesenchymal stem cells migrated toward the cathode, whereas macrophages toward the anode. Analysis of intracellular pathways revealed that macrophage electrotaxis mostly depended on Rho family small GTPases and calcium ions, but interruption of PI3K and Arp2/3 had the most pronounced effect on electrotaxis of MSCs. However, in all cases we observed only a partial decrease in directionality of cell movement after inhibition of certain proteins. Additionally, although we noticed the accumulation of EGFR at the cathodal side of MSCs, it was not involved in electrotaxis. Moreover, the cell reaction to EF was very dynamic with first symptoms occurring within <1min. In conclusion, the physiological DC-EF may act as a factor positioning bone marrow cells within a wound bed and the opposite direction of MSC and macrophage movement did not result either from utilizing different signalling or redistribution of investigated cell surface receptors.


Asunto(s)
Células de la Médula Ósea/citología , Electricidad , Células Madre Mesenquimatosas/citología , Piel/lesiones , Cicatrización de Heridas , Animales , Células de la Médula Ósea/metabolismo , Calcio/metabolismo , Movimiento Celular , Receptores ErbB/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Transducción de Señal
5.
Acta Pol Pharm ; 74(1): 111-117, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29474767

RESUMEN

Recently we described a group of purine derivatives based on theophylline structure with acetic acid moiety. Studies in a group of these compounds demonstrated their analgesic and anti-inflammatory properties. Taking into account wide spectrum of theophylline derivatives activity and searching for their new properties. the aim of the study was to evaluate safety of newly synthesized derivatives in human keratinocytes model. The effect of new purine derivatives with acetic acid moiety: 2-(8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl) acetic acid and 2-(1,3-dimethyl-2,6,8-trioxo-9H-purin-7-yl) acetic acid on proliferation rate and the ability of keratinocytes to migration was carried out. The results clearly demonstrate that purine derivatives with acetic acid moiety did not affect basic keratinocytes functions. Our compounds do not inhibit cells proliferation rate as well as their ability to migration. It can be therefore concluded that new purine derivatives with acetic acid moiety are safe versus normal cells. This observation opens up additional prospects in searching for their new applications.


Asunto(s)
Queratinocitos/efectos de los fármacos , Purinas/farmacología , Ácido Acético/farmacología , Analgésicos/farmacología , Antiinflamatorios/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Purinas/toxicidad
6.
Cell Mol Biol Lett ; 19(2): 297-314, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24825569

RESUMEN

Degradable aliphatic polyesters such as polylactides, polyglycolides and their copolymers are used in several biomedical and pharmaceutical applications. We analyzed the influence of poly(L-lactide-co-glycolide) (PLGA) thin films on the adhesion, proliferation, motility and differentiation of primary human skin keratinocytes and fibroblasts in the context of their potential use as cell carriers for skin tissue engineering. We did not observe visible differences in the morphology, focal contact appearance, or actin cytoskeleton organization of skin cells cultured on PLGA films compared to those cultured under control conditions. Moreover, we did not detect biologically significant differences in proliferative activity, migration parameters, level of differentiation, or expression of vinculin when the cells were cultured on PLGA films and tissue culture polystyrene. Our results indicate that PLGA films do not affect the basic functions of primary human skin keratinocytes and fibroblasts and thus show acceptable biocompatibility in vitro, paving the way for their use as biomaterials for skin tissue engineering.


Asunto(s)
Materiales Biocompatibles/química , Ácido Láctico/química , Ácido Poliglicólico/química , Ingeniería de Tejidos , Citoesqueleto de Actina/efectos de los fármacos , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Ácido Láctico/síntesis química , Ácido Láctico/farmacología , Ácido Poliglicólico/síntesis química , Ácido Poliglicólico/farmacología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Regeneración/efectos de los fármacos , Piel/metabolismo , Propiedades de Superficie , Vinculina/metabolismo
7.
Med Sci Monit ; 20: 91-6, 2014 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-24448309

RESUMEN

BACKGROUND: Cutaneous wound healing results in scar formation. Matrix metalloproteinases (MMP) transform extracellular matrix proteins and modulate inflammation and cell signaling, thus determining scar outcome. To provide rapid wound closure and reduced scarring, dermal scaffolds were introduced. Little is known about the influence of these materials on MMPs levels. MATERIAL AND METHODS: In this in vivo study the levels of MMP-2, MMP-9, and mediators of inflammation and fibrosis (IL-4 and TGF-beta1) in patients treated with Integra® dermal regeneration template (IDRT) were investigated. In the group of 11 pediatric patients treated with IDRT, levels of selected molecules were analyzed before surgery and at day 1, 7, and 25 after scaffold implantation. RESULTS: The mean IDRT take rate was 89.5 ± 4.7% with 4 patients (36%) who developed local infection. Patients were divided into 2 groups according to presence of infection (1 group with complications and 1 group without complications). In the group with complications, the IDRT take rate was significantly reduced compared to the group without complications (71.5 ± 5.4 vs. 100 ± 0.1; p<0.005). Plasma levels of MMP-2 were significantly (p<0.05) elevated in both groups on day 7 after the scaffold placement compared to baseline. Positive correlations between IL-4 and MMP-2 (p=0.01) in the group with complications and TGF-beta1 and MMP-9 (p=0.012) in both groups were observed. CONCLUSIONS: These findings suggest that Integra® scaffold degradation is mainly caused by MMP-2, whereas inflammation associated with local infection increases levels of this molecule and it is not associated with elevation of MMP-9. This shows that dermal regeneration with Integra® uses molecular mechanisms other than scar formation during dermal wound healing.


Asunto(s)
Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Regeneración/fisiología , Fenómenos Fisiológicos de la Piel , Piel/lesiones , Andamios del Tejido , Cicatrización de Heridas/fisiología , Dermis Acelular/metabolismo , Femenino , Humanos , Masculino
8.
Przegl Lek ; 71(6): 334-9, 2014.
Artículo en Polaco | MEDLINE | ID: mdl-25344975

RESUMEN

Cartilage reconstruction is a crucial issue for tissue engineering because of high damage frequency in connection with low regenerative capacity. Microfractures and shaving are the oldest and most commonly used practices. The newest techniques are: Autologous Chondrocyte Implantation, Matrix Associated Chondrocytes Implantation and their derivatives. Dedifferentiation of chondrocytes due to low proliferation rate and phenotype loss makes isolation and in vitro culture of normal human chondrocytes very complex. Therefore, obtaining mesenchymal stem cells from various sources and differentiating them into chondrocytes is another interesting approach.


Asunto(s)
Cartílago/cirugía , Condrocitos/citología , Condrocitos/trasplante , Medicina Regenerativa/métodos , Ingeniería de Tejidos/métodos , Artroplastia Subcondral , Cartílago/lesiones , Técnicas de Cultivo de Célula/métodos , Diferenciación Celular , Humanos , Trasplante de Células Madre Mesenquimatosas
9.
Postepy Dermatol Alergol ; 31(3): 164-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25097488

RESUMEN

INTRODUCTION: The local treatment in burns larger than 50% of total body surface area is still the great challenge for surgeons. AIM: This paper presents a review of different solutions for deep burn wound healing in children and the early outcomes of treatment with combined autologous cell culture technique. MATERIAL AND METHODS: For this study, 20 children aged between 4 and 12 years with 55-65% of TBSA III grade burn injury were analyzed. A skin sample, 1 cm × 1 cm in size, for keratinocyte cultivation, was taken on the day of the burn. After necrotic tissue excision, the covering of the burned area with an isolated meshed skin graft was carried out between day 4 and 7. After 7 days of keratinocyte cultivation, the mentioned areas were covered with cells from the culture. We divided the burned regions, according to the way of wound closure, into 3 groups each consisting of 15 treated regions of the body. We used meshed split thickness skin grafts (SSG group), cultured autologous keratinocytes (CAC group), and both techniques applied in one stage (SSG + CAC group). RESULTS: In the SSG group, the mean time for complete closure of wounds was 12.7 days. Wounds treated with CAC only needed a non-significantly longer time to heal - 14.2 days (p = 0.056) when compared to SSG. The shortest time to heal was observed in the group treated with SSG + CAC - 8.5 days, and it was significantly shorter when compared to the SSG and CAC groups (p < 0.001). CONCLUSIONS: This study suggests that cultured keratinocytes obtained after short-time multiplication, combined with meshed autologous split thickness skin grafts, constitute the optimal wound closure in burned children.

10.
Biol Chem ; 394(1): 113-23, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23091270

RESUMEN

Silver nanoparticles (AgNPs) have many biological applications in biomedicine, biotechnology and other life sciences. Depending on the size, shape and the type of carrier, AgNPs demonstrate different physical and chemical properties. AgNPs have strong antimicrobial, antiviral and antifungal activity, thus they are used extensively in a range of medical settings, particularly in wound dressings but also in cosmetics. This study was undertaken to examine the potential toxic effects of 15 nm polyvinylpyrrolidone-coated AgNPs on primary normal human epidermal keratinocytes (NHEK). Cells were treated with different concentrations of AgNPs and then cell viability, metabolic activity and other biological and biochemical aspects of keratinocytes functioning were studied. We observed that AgNPs decrease keratinocyte viability, metabolism and also proliferatory and migratory potential of these cells. Moreover, longer exposure resulted in activation of caspase 3/7 and DNA damage. Our studies show for the first time, that AgNPs may present possible danger for primary keratinocytes, concerning activation of genotoxic and cytotoxic processes depending on the concentration.


Asunto(s)
Queratinocitos/efectos de los fármacos , Nanopartículas del Metal/química , Plata/farmacología , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Daño del ADN , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Humanos , Queratinocitos/metabolismo , Plata/química , Relación Estructura-Actividad
11.
Cannabis Cannabinoid Res ; 8(5): 779-789, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-36318796

RESUMEN

Objective: Osteoarthritis (OA) is common degenerative joint disease, mostly characterized by gradual cartilage breakdown. Currently there are no disease-modifying drugs available, therefore, there is an increasing need for basic research to focus on cartilage function in OA. Changes in cannabinoid receptor 2 (CB2) expression were observed in the OA-affected joints, although its action on cartilage chondrocytes remain unclear. We studied the action of dimethylbutyl-deoxy-delta-8-THC (JWH-133), selective CB2 agonist, on chondrocytes metabolism using both in vitro and in vivo studies. Design: Intraarticular (i.a.) injection of monoiodoacetate (MIA) was used to induce OA in rats. OA-related pain symptoms were assessed by pressure application measurements (PAMs). Primary human chondrocytes treated with MIA were used to investigate action of JWH-133 on chondrocytes viability, proliferation, and motility. Cannabinoid system components, inflammatory cytokines and metalloproteinases (MMPs) expression was measured on messenger RNA and protein levels in chondrocytes and animal cartilage. Results: Repeated, i.a. administration of JWH-133 showed antinociceptive potential in PAM, as well as decreased levels of MMPs, which suggests that CB2 agonism may modify degradation of cartilage. JWH-133 administration partially reduced toxicity, increased proliferation, and chondrocytes' migration. Moreover, our data suggest that CB2 agonism leads to alleviation of MMPs expression both in vitro and in vivo. Conclusions: In this study, we demonstrate modifying effect of JWH-133 local administration on cartilage metabolism and MMP13 expression that was shown to be involved in cartilage degradation. CB2 receptors' activation may be of benefit for chondrocytes' proliferation, therefore delaying disease progression. Our results propose direction of studies on OA-modifying treatment that can benefit in management of human OA.


Asunto(s)
Cannabinoides , Cartílago Articular , Osteoartritis , Ratas , Humanos , Animales , Cartílago Articular/metabolismo , Metaloproteasas/metabolismo , Metaloproteasas/farmacología , Metaloproteasas/uso terapéutico , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Osteoartritis/metabolismo , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Regeneración
12.
iScience ; 26(3): 106195, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36890793

RESUMEN

Aberrant mechanotransduction and compromised epithelial barrier function are associated with numerous human pathologies including inflammatory skin disorders. However, the cytoskeletal mechanisms regulating inflammatory responses in the epidermis are not well understood. Here we addressed this question by inducing a psoriatic phenotype in human keratinocytes and reconstructed human epidermis using a cytokine stimulation model. We show that the inflammation upregulates the Rho-myosin II pathway and destabilizes adherens junctions (AJs) promoting YAP nuclear entry. The integrity of cell-cell adhesion but not the myosin II contractility per se is the determinative factor for the YAP regulation in epidermal keratinocytes. The inflammation-induced disruption of AJs, increased paracellular permeability, and YAP nuclear translocation are regulated by ROCK2, independently from myosin II activation. Using a specific inhibitor KD025, we show that ROCK2 executes its effects via cytoskeletal and transcription-dependent mechanisms to shape the inflammatory response in the epidermis.

13.
Biomedicines ; 11(10)2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37893027

RESUMEN

Although the impact of age, gender, and obesity on the skin wound healing process has been extensively studied, the data related to gender differences in aspects of skin scarring are limited. The present study performed on abdominal human intact and scar skin focused on determining gender differences in extracellular matrix (ECM) composition, dermal white adipose tissue (dWAT) accumulation, and Foxn1 expression as a part of the skin response to injury. Scar skin of men showed highly increased levels of COLLAGEN 1A1, COLLAGEN 6A3, and ELASTIN mRNA expression, the accumulation of thick collagen I-positive fibers, and the accumulation of α-SMA-positive cells in comparison to the scar skin of women. However, post-injured skin of women displayed an increase (in comparison to post-injured men's skin) in collagen III accumulation in the scar area. On the contrary, women's skin samples showed a tendency towards higher levels of adipogenic-related genes (PPARγ, FABP4, LEPTIN) than men, regardless of intact or scar skin. Intact skin of women showed six times higher levels of LEPTIN mRNA expression in comparison to men intact (p < 0.05), men post-injured (p < 0.05), or women post-injured scar (p < 0.05) skin. Higher levels of FOXN1 mRNA and protein were also detected in women than in men's skin. In conclusion, the present data confirm and extend (dWAT layer) the data related to the presence of differences between men and women in the skin, particularly in scar tissues, which may contribute to the more effective and gender-tailored improvement of skin care interventions.

14.
Cell Mol Biol Lett ; 16(3): 412-30, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21614489

RESUMEN

Published data concerning the effects of hypertonicity on cell motility have often been controversial. The interpretation of results often rests on the premise that cell responses result from cell dehydration, i.e. osmotic effects. The results of induced hypertonicity on cell movement of Dictyostelium discoideum amoebae and human melanoma HTB-140 cells reported here show that: i) hypertonic solutions of identical osmolarity will either inhibit or stimulate cell movement depending on specific solutes (Na(+) or K(+), sorbitol or saccharose); ii) inhibition of cell motility by hypertonic solutions containing Na(+) ions or carbohydrates can be reversed by the addition of calcium ions; iii) various cell types react differently to the same solutions, and iv) cells can adapt to hypertonic solutions. Various hypertonic solutions are now broadly used in medicine and to study modulation of gene expression. The observations reported suggest the need to examine whether the other responses of cells to hypertonicity can also be based on the solute-dependent cell responses besides cell dehydration due to the osmotic effects.


Asunto(s)
Carcinoma 256 de Walker/patología , Movimiento Celular/efectos de los fármacos , Dictyostelium/citología , Dictyostelium/efectos de los fármacos , Soluciones Hipertónicas/farmacología , Melanoma/patología , Actinas/metabolismo , Animales , Cloruro de Calcio/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Extensiones de la Superficie Celular/efectos de los fármacos , Humanos , Cinética , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Ratas , Cloruro de Sodio/farmacología , Sorbitol/farmacología , Sacarosa/farmacología
15.
Biomolecules ; 11(6)2021 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-34064164

RESUMEN

Skin barrier damage can be the result of various external factors including heat, radiation, chemicals and many others. Any interruption of the skin barrier integrity causes the exposure of the organism to harmful environmental factors. Therefore, there is an urgent need to develop novel therapeutics characterized by high bioavailability and effectiveness in skin damage recovery. Birch bark is known as a clinically proven, traditional medicinal remedy to accelerate wound healing. Lupeol, one of the main birch bark ingredients, shows a wide range of biological activity beneficial to the skin. The purpose of the research was to determine the influence of new lupeol derivatives on keratinocyte and fibroblast migration and proliferation, as well as to investigate various mechanisms of their antioxidant activity. The chemical modification of lupeol structure was intended to obtain more effective therapeutics characterized by higher bioavailability, permeability and safety of use. The novel triterpenes presented in this study were evaluated as the potential active ingredients preventing skin tissue degradation. Lupeol esters influence skin cells' motility and proliferation. Importantly, they are able to reduce reactive oxygen species and act indirectly by protecting the skin protein structure from being oxidized by free radicals.


Asunto(s)
Antioxidantes , Queratinocitos , Triterpenos Pentacíclicos , Piel , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Humanos , Queratinocitos/metabolismo , Queratinocitos/patología , Triterpenos Pentacíclicos/síntesis química , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacología , Piel/lesiones , Piel/metabolismo , Piel/patología , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología
16.
Sci Total Environ ; 765: 142670, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33069473

RESUMEN

Toxins produced by cyanobacteria (cyanotoxins) are among the most dangerous natural compounds. In recent years, there have been many published papers related to the toxic alkaloids cylindrospermopsin (CYN) and anatoxin-a (ANTX-a), which are synthesized by several freshwater species of cyanobacteria (i.e. Raphidiopsis raciborskii and Anabaena flos-aquae) and are some of the most common cyanotoxins in aquatic reservoirs. The harmful properties of CYN are wide and primarily include cytotoxicity. To date, several analogs and decomposition products of CYN have been described, which can potentially increase its toxic effects in living organisms. The mode of action of ANTX-a is different than that observed after CYN exposure and involves structures in the nervous system. One of the most frequent situations in which cyanotoxins are introduced into the human body is by skin contact with contaminated water, i.e., during water sports, fishing or agriculture. Unfortunately, to date, knowledge on the influence of CYN, its decomposition products, and ANTX-a on human skin is limited. In this paper, we investigated the impact of CYN, its decomposition products, and ANTX-a on the proliferation of human keratinocytes, which provide a protective barrier on the skin. Moreover, we described the cytotoxic effects developed in the selected cell type and estimated the ability of the keratinocytes to migrate under the influence of the studied cyanotoxins. The obtained results suggest that CYN and its decomposition products at concentrations corresponding to that determined for CYN in nature (1 µg·mL-1) are strong inhibitors of keratinocyte proliferation (70% inhibition within 24 h for pure CYN). The cytotoxic effects of CYN and the CYN decomposition products on keratinocytes was also significant, and the pure toxin (1 µg·mL-1) was estimated to be 35% after 24 h of exposure. Similarly, harmful effects caused by CYN and its byproducts were observed during keratinocyte migration, and the initial form of the toxin (1 µg·mL-1) showed 40% inhibition within 16 h. Different results were obtained for ANTX-a. The toxic effects of this compound on human keratinocytes estimated by the applied tests was observed only at the highest tested concentration (10 µg·mL-1) and after a long period of exposure. The results presented in this paper are, to the best of our knowledge, the first description of the influence of CYN, CYN decomposition products, and ANTX-a on human epidermal cells. Clearly, CYN and its decomposition products are serious threats not only when acting on internal organs but also during the skin contact stage. Further studies on cyanotoxins should focus on the determination of their decomposition products and ecotoxicology in natural aquatic environments.


Asunto(s)
Queratinocitos , Microcistinas , Alcaloides , Toxinas de Cianobacterias , Cylindrospermopsis , Humanos , Tropanos
17.
Mol Cancer ; 9: 159, 2010 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-20569465

RESUMEN

BACKGROUND: Glioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARalpha) that can switch energy metabolism from glycolysis to fatty acid beta-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal. METHODS: The effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARalpha activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were analyzed in human glioma cell lines. RESULTS: Fenofibrate treatment attenuated IGF-I signaling responses and repressed cell motility of LN-229 and T98G Glioma cell lines. In the absence of fenofibrate, specific inhibition of the IGF-IR had only modest effects on Glioma cell motility. Further experiments revealed that PPARalpha-dependent accumulation of ROS is a strong contributing factor in Glioma cell lines responses to fenofibrate. The ROS scavenger, N-acetyl-cysteine (NAC), restored cell motility, improved mitochondrial potential, and increased ATP levels in fenofibrate treated Glioma cell lines. CONCLUSIONS: Our results indicate that although fenofibrate-mediated inhibition of the IGF-IR may not be sufficient in counteracting Glioma cell dispersal, PPARalpha-dependent metabolic switch and the resulting ROS accumulation strongly contribute to the inhibition of these devastating brain tumor cells.


Asunto(s)
Neoplasias Encefálicas/patología , Fenofibrato/farmacología , Glioma/patología , PPAR alfa/fisiología , Especies Reactivas de Oxígeno/metabolismo , Receptor IGF Tipo 1/antagonistas & inhibidores , Adenosina Trifosfato/biosíntesis , Secuencia de Bases , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Glioma/metabolismo , Humanos , ARN Interferente Pequeño
18.
Int J Cancer ; 127(11): 2554-68, 2010 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-20162608

RESUMEN

We have demonstrated that the α-chemokine stromal-derived factor (SDF)-1-CXCR4 axis plays an important role in rhabdomyosarcoma (RMS) metastasis. With the recent description of CXCR7, a new receptor for SDF-1 that also binds the interferon-inducible T-cell α chemoattractant (ITAC) chemokine, we became interested in the role of the CXCR7-SDF-1/ITAC axis in RMS progression. To address this issue, we evaluated 6 highly metastatic alveolar (A)RMS and 3 less metastatic embryonal (E)RMS cell lines and found that all these cell lines express CXCR7. Although CXCR4 was expressed at a much higher level by highly metastatic ARMS lines, CXCR7 was present at a high level on ERMS lines. We also noticed that CXCR7 expression on RMS cells was downregulated in hypoxic conditions. More importantly, the CXCR7 receptor on RMS cell lines was functional after stimulation with ITAC and SDF-1 as evidenced by mitogen-activated protein kinase (MAPK)p42/44 and AKT phosphorylation as well as CXCR7 internalization, chemotaxis, cell motility and adhesion assays. Similarly to CXCR4, signaling from activated CXCR7 was not associated with increased RMS proliferation or cell survival. Moreover, CXCR7(+) RMS cells responded to SDF-1 and I-TAC in the presence of CXCR4 antagonists (T140, AMD3100). Furthermore, while intravenous injection of RMS cells with overexpressed CXCR7 resulted in increased seeding efficiency of tumor cells to bone marrow, CXCR7 downregulation showed the opposite effect. In conclusion, the CXCR7-SDF-1/ITAC axis is involved in the progression of RMS; targeting of the CXCR4-SDF-1 axis alone without simultaneous blockage of CXCR7 will be an inefficient strategy for inhibiting SDF-1-mediated prometastatic responses of RMS cells.


Asunto(s)
Quimiocina CXCL11/metabolismo , Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Rabdomiosarcoma Alveolar/metabolismo , Rabdomiosarcoma Embrionario/metabolismo , Animales , Bencilaminas , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Procesos de Crecimiento Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Ciclamas , Regulación hacia Abajo , Células Endoteliales/patología , Fibronectinas/metabolismo , Compuestos Heterocíclicos/farmacología , Humanos , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones SCID , Oligopéptidos/farmacología , Toxina del Pertussis/farmacología , Fosforilación , Receptores CXCR/biosíntesis , Receptores CXCR4/antagonistas & inhibidores , Rabdomiosarcoma Alveolar/patología , Rabdomiosarcoma Embrionario/patología , Inhibidores Tisulares de Metaloproteinasas/metabolismo
19.
Przegl Lek ; 67(7): 512-8, 2010.
Artículo en Polaco | MEDLINE | ID: mdl-21387766

RESUMEN

A historical outline of the immunosuppressive treatment and related developments in transplantology is presented here. It is accompanied by a description of the essential knowledge of the bone marrow histology as well as of the role of mesenchymal stem cells (MSCs) in the regenerative processes occurring in the organism following tissue damage. We have reviewed contemporary knowledge of negative (quantitative and qualitative) changes in bone tissues caused by immunosuppressive treatment after an organ transplantation and mentioned prophylactic measures which may be used in such cases. We also describe basic immunosuppressive medications taking into account their side effects on the organism of the patient and, in particular, on the bone marrow metabolism as well as the mechanisms of their action at the cellular level.


Asunto(s)
Médula Ósea/metabolismo , Huésped Inmunocomprometido/fisiología , Inmunosupresores/farmacología , Trasplante de Órganos , Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Trasplantes
20.
Bioengineering (Basel) ; 7(3)2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32630660

RESUMEN

Fibrosis of burn-related wounds remains an unresolved clinical issue that leads to patient disability. The aim of this study was to assess the efficacy of the transplantation of adipose-derived stromal cells seeded onto a collagen-based matrix in the reconstruction of burn-related scars. Here, we characterized an in vitro interaction between adipose-derived stromal cells and a collagen-based matrix, Integra®DRT. Our results show that transcription of pro-angiogenic, remodeling, and immunomodulatory factors was more significant in adipose-derived stromal cells than in fibroblasts. Transcription of metalloproteinases 2 and 9 is positively correlated with the collagenolytic activity of the adipose-derived stromal cells seeded onto Integra®DRT. The increase in the enzymatic activity corresponds to the decrease in the elasticity of the whole construct. Finally, we validated the treatment of a post-excision wound using adipose-derived stromal cells and an Integra®DRT construct in a 25-year-old woman suffering from burn-related scars. Scarless healing was observed in the area treated by adipose-derived stromal cells and the Integra®DRT construct but not in the reference area where Integra®DRT was applied without cells. This clinical observation may be explained by in vitro findings: Enhanced transcription of the vascular endothelial growth factor as well as remodeling of the collagen-based matrix decreased mechanical stress. Our experimental treatment demonstrated that the adipose-derived stromal cells seeded onto Integra®DRT exhibit valuable properties that may improve post-excision wound healing and facilitate skin regeneration without scars.

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