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1.
Materials (Basel) ; 14(9)2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33923213

RESUMEN

BACKGROUND: The biological factors involved in dental implant osseointegration need to be investigated to improve implant success. METHODS: Twenty-four implants were inserted into the tibias of six minipigs. Bone samples were obtained at 7, 14, and 56 days. Biomolecular analyses evaluated mRNA of BMP-4, -7, Transforming Growth Factor-ß2, Interleukin-1ß, and Osteocalcin in sites treated with rhBMP-7, Type 1 Collagen, or Fibronectin (FN). Inflammation and osteogenesis were evaluated by histological analyses. RESULTS: At 7 and 14 days, BMP-4 and BMP-7 increased in the sites prepared with rhBMP-7 and FN. BMP-7 remained greater at 56 days in rhBMP-7 and FN sites. BPM-4 at 7 and 14 days increased in Type 1 Collagen sites; BMP-7 increased from day 14. FN increased the TGF-ß2 at all experimental times, whilst the rhBMP-7 only did so up to 7 days. IL-1ß increased only in collagen-treated sites from 14 days. Osteocalcin was high in FN-treated sites. Neutrophilic granulocytes characterized the inflammatory infiltrate at 7 days, and mononuclear cells at 14 and 56 days. CONCLUSIONS: This initial pilot study, in a novel way, evidenced that Type 1 Collagen induced inflammation and did not stimulate bone production; conversely FN or rhBMP-7 showed neo-osteogenetic and anti-inflammatory properties when directly added into implant bone site.

2.
Chem Biol Interact ; 292: 9-14, 2018 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-29986832

RESUMEN

Breast cancer chemotherapy can cause side effects due to nonspecific drug delivery, low solubility and fast metabolism of drugs used in conventional therapy. Moreover, the therapeutic effect of the drugs is often reduced by the strengthening of chemoresistance, which occurs via a variety of mechanisms. Different strategies have been developed to reduce multidrug resistance (MDR)-associated gene expressions including the use of surfactants and polymers. In this study superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with conjugated linoleic acid (CLA) reduced the number and viability of cells in comparison with both untreated cells or cells treated with SPIONs alone. This cytostatic effect correlated with the increase of peroxisome proliferator-activated receptors γ (PPARγ). The necrotic cell death induced, as a consequence, an inflammatory process, as evidenced by the decrease of the anti-inflammatory PPARα and increase of pro-inflammatory TNFα and IL-1ß. PPARs were examined because CLA is one of their natural ligands. The antitumor effect observed was accompanied by a down-regulation of p-glycoprotein (P-gp), which was the first important discovered efflux transporter belonging to MDR, and of ALDH3A1, an enzyme able to metabolize some drugs, reducing their effects. The down-regulation of P-gp correlated with the increase of cytokines. The ALDH3A1 decrease correlated with the increase of PPARγ. Based on these results, PPARs are molecular mediators of anti-cancer effect of SPIONs functionalized with CLA, being changes in these nuclear receptors correlated with induction of cytotoxicity and inflammation, and decreased ability of cancer cells in blocking anti-cancer drug effect.


Asunto(s)
Antineoplásicos/farmacología , Ácidos Linoleicos Conjugados/química , Nanopartículas de Magnetita/química , Receptores Activados del Proliferador del Peroxisoma/farmacología , Anilidas/farmacología , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Femenino , Interleucina-1beta/metabolismo , Ácidos Linoleicos Conjugados/uso terapéutico , Nanopartículas de Magnetita/uso terapéutico , Ratones , Factor de Necrosis Tumoral alfa/metabolismo
4.
Mater Sci Eng C Mater Biol Appl ; 76: 439-447, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28482548

RESUMEN

One of the goals for the development of more effective cancer therapies with reduced toxic side effects is the optimization of innovative treatments to selectively kill tumor cells. The use of nanovectors loaded with targeted therapeutic payloads is one of the most investigated strategies. In this paper superparamagnetic iron oxide nanoparticles (SPIONs) coated by a silica shell or uncoated, were functionalized with single-layer and bi-layer conjugated linoleic acid (CLA). Silica was used to protect the magnetic core from oxidation, improve the stability of SPIONs and tailor their surface reactivity. CLA was used as novel grafting biomolecule for its anti-tumor activity and to improve particle dispersibility. Mouse breast cancer 4T1 cells were treated with these different SPIONs. SPIONs functionalized with the highest quantity of CLA and coated with silica shell were the most dispersed. Cell viability was reduced by SPIONs functionalized with CLA in comparison with cells which were untreated or treated with SPIONs without CLA. As regards the types of SPIONs functionalized with CLA, the lowest viability was observed in cells treated with uncoated SPIONs with the highest quantity of CLA. In conclusion, the silica shell free SPIONs functionalized with the highest amount of CLA can be suggested as therapeutic carriers because they have the best dispersion and ability to decrease 4T1 cell viability.


Asunto(s)
Nanopartículas de Magnetita , Animales , Supervivencia Celular , Humanos , Hierro , Ácido Linoleico , Ratones , Neoplasias , Dióxido de Silicio
5.
J Biomed Mater Res B Appl Biomater ; 105(6): 1586-1593, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-27126254

RESUMEN

Hernias are generally repaired using synthetic prostheses. Infection may already be present or develop during implantation. Based on the increasing resistance to antibiotics, and the well-known antimicrobial properties of silver (Ag), the possibility of coating hernia prostheses with a nanostructured layer containing Ag was explored. Prostheses (Clear Mesh Composite [CMC]) made up of two polypropylene layers (macroporous light mesh and thin transparent film) were tested with human mesothelial cells from omentum biopsies. Mesotheliocytes modulate abdominal wall healing producing cytokines, growth factors, and adhesion molecules. Evaluating the growth of these cells on CMC or film alone showed that cell numbers on CMC increased over time, and were higher than those on film alone. Vimentin immunostaining confirmed the cells to be mesotheliocytes. Subsequently, the biocompatibility of mesh layer, coated or not with a thin layer of Ag/SiO2 -nanoclusters, was analyzed, showing no difference in absence or presence of Ag/SiO2 . Differently, TGF-ß2 production, involved in tissue repair and fibrosis, increased in the presence of Ag/SiO2 . Moreover, Ag/SiO2 -coated mesh showed antibacterial properties. In conclusion, the mesh layer coated with Ag/SiO2 afforded cell growth, and showed antibacterial activity. Coating only the mesh layer did not decrease film transparency, and did not favor the formation of adhesions on the visceral side. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1586-1593, 2017.


Asunto(s)
Materiales Biocompatibles Revestidos , Hernia , Herniorrafia , Implantes Experimentales , Ensayo de Materiales , Peritoneo/metabolismo , Polipropilenos , Dióxido de Silicio , Plata , Mallas Quirúrgicas , Células Cultivadas , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Epitelio/metabolismo , Femenino , Humanos , Masculino , Peritoneo/citología , Polipropilenos/química , Polipropilenos/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Plata/química , Plata/farmacología
6.
Antioxidants (Basel) ; 5(1)2016 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-26907355

RESUMEN

In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations.

7.
Biomed Res Int ; 2015: 642520, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26301250

RESUMEN

BACKGROUND: This study investigated whether the 1 : 2 ω-3/ω-6 ratio may reduce proinflammatory response in human alveolar cells (A549) exposed to an ex vivo inflammatory stimulus (bronchoalveolar lavage fluid (BALF) of acute respiratory distress syndrome (ARDS) patients). Methods. We exposed A549 cells to the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA) were added as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in two ratios (1 : 2 or 1 : 7). 24 hours later, in culture supernatants were evaluated cytokines (TNF-α, IL-6, IL-8, and IL-10) and prostaglandins (PGE2 and PGE3) release. The FA percentage content in A549 membrane phospholipids, content of COX-2, level of PPARγ, and NF-κB binding activity were determined. RESULTS: The 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the cell membranes (P < 0.001). The proinflammatory cytokine release was reduced by the 1 : 2 ratio (P < 0.01 to <0.001) but was increased by the 1 : 7 ratio (P < 0.01). The 1 : 2 ratio reduced COX-2 and PGE2 (P < 0.001) as well as NF-κB translocation into the nucleus (P < 0.01), while it increased activation of PPARγ and IL-10 release (P < 0.001). Conclusion. This study demonstrated that shifting the FA supply from ω-6 to ω-3 decreased proinflammatory mediator release in human alveolar cells exposed to BALF of ARDS patients.


Asunto(s)
Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Mediadores de Inflamación/farmacología , Inflamación/dietoterapia , Síndrome de Dificultad Respiratoria/dietoterapia , Ácido Araquidónico/administración & dosificación , Líquido del Lavado Bronquioalveolar/química , Ciclooxigenasa 2/biosíntesis , Dinoprostona/biosíntesis , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/genética , Inflamación/metabolismo , Mediadores de Inflamación/química , Interleucina-10/biosíntesis , FN-kappa B/biosíntesis , PPAR gamma/biosíntesis , Alveolos Pulmonares/química , Alveolos Pulmonares/metabolismo , Síndrome de Dificultad Respiratoria/genética , Síndrome de Dificultad Respiratoria/metabolismo
8.
Mater Sci Eng C Mater Biol Appl ; 38: 107-18, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24656359

RESUMEN

A glass belonging to the system SiO2-P2O5-CaO-MgO-Na2O-K2O was modified by introducing two different amounts of manganese oxide (MnO). Mn-doped glasses were prepared by melt and quenching technique and characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM) observation and energy dispersion spectrometry (EDS) analysis. In vitro bioactivity test in simulated body fluid (SBF) showed a slight decrease in the reactivity kinetics of Mn-doped glasses compared to the glass used as control; however the glasses maintained a good degree of bioactivity. Mn-leaching test in SBF and minimum essential medium (MEM) revealed fluctuating trends probably due to a re-precipitation of Mn compounds during the bioactivity process. Cellular tests showed that all the Mn-doped glasses, up to a concentration of 50 µg/cm(2) (µg of glass powders/cm(2) of cell monolayer), did not produce cytotoxic effects on human MG-63 osteoblasts cultured for up to 5 days. Finally, biocompatibility tests demonstrated a good osteoblast proliferation and spreading on Mn-doped glasses and most of all that the Mn-doping can promote the expression of alkaline phosphatase (ALP) and some bone morphogenetic proteins (BMPs).


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Vidrio/química , Manganeso/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Cristalización , Análisis Diferencial Térmico , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , L-Lactato Deshidrogenasa/metabolismo , Malondialdehído/metabolismo , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/ultraestructura , Polvos , Espectrometría por Rayos X , Temperatura de Transición , Difracción de Rayos X
9.
Clin Oral Investig ; 17(4): 1259-66, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22864527

RESUMEN

OBJECTIVES: The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget's disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa "in vivo." PATIENTS AND METHODS: Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF). RESULTS: Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased. CONCLUSIONS: Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio. CLINICAL RELEVANCE: The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/metabolismo , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Células Endoteliales/fisiología , Imidazoles/efectos adversos , Mucosa Bucal/metabolismo , Osteoclastos/fisiología , Anciano , Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Casos y Controles , Proliferación Celular , Citocinas/metabolismo , Difosfonatos/administración & dosificación , Femenino , Líquido del Surco Gingival/química , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Imidazoles/administración & dosificación , Inyecciones Intravenosas/efectos adversos , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Mieloma Múltiple/tratamiento farmacológico , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Estadísticas no Paramétricas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ácido Zoledrónico
10.
Lasers Med Sci ; 27(2): 353-9, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21279404

RESUMEN

Alveolar healing following tooth extraction is a complex repair process involving different tissues, including epithelium and bone. This research aimed to study the effect of laser therapy on alveolar healing process in patients waiting for liver transplantation, evaluating some inflammation, osteogenesis, and clinical parameters. Twelve patients with hepatic failure waiting for liver transplantation, with indications to bilateral extraction, entered the split-mouth study. One post-extractive defect was treated with laser while the other was left without treatment. Specimens of soft tissues were removed from around the tooth before extraction and after 7 days. Superpulsed laser irradiation prevented IL-1ß increase and induced IL-6, IL-10, and collagen III increase at 7 days in comparison to their level before extraction, whereas the other parameters were unmodified. Moreover, the epithelial regeneration evidenced a positive result of laser therapy, and the patients reported less pain in the site treated with laser. In conclusion, laser therapy appears to be the treatment of choice for patients due to its clinical efficacy, safety, good tolerance, and its ability to prevent inflammation.


Asunto(s)
Proceso Alveolar/efectos de la radiación , Terapia por Láser , Fallo Hepático/complicaciones , Osteogénesis/efectos de la radiación , Extracción Dental , Cicatrización de Heridas/efectos de la radiación , Citocinas/metabolismo , Colágenos Fibrilares/metabolismo , Humanos , Fallo Hepático/fisiopatología , Trasplante de Hígado , Reacción en Cadena en Tiempo Real de la Polimerasa , Cicatrización de Heridas/fisiología
11.
Photomed Laser Surg ; 29(8): 565-71, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21631375

RESUMEN

OBJECTIVE: This research studied the effects of laser therapy on healing processes following tooth extraction in healthy human subjects, evaluating some inflammation, osteogenesis, and clinical parameters. BACKGROUND DATA: Alveolar healing following tooth extraction is a complex repair process involving different types of tissues, including epithelium and bone. Therefore, it can be advantageous to use techniques able to influence the healing of all tissues. PATIENTS AND METHODS: Ten healthy human subjects with indications for bilateral tooth extraction entered the split-mouth study. The subject/patient becomes his/her own control, thereby eliminating all individual differences in response to laser treatment. This consisted of: 904-nm laser, 33 W peak power, 30 KHz, 200 ns, average power 200 mW, illuminated area 1 cm(2), 200 mW/cm(2), 15 min, 180 J, 180 J/cm(2). In each patient, one post-extraction site was treated with laser radiation, whereas the other was left untreated as a control. Soft-tissue specimens were removed from the extraction site before tooth extraction (T0) and 7 days after from extraction (T7); expression of inflammatory and osteogenesis parameters was evaluated on these specimens. The clinical parameter "pain" was evaluated for each subject. RESULTS: Superpulsed laser irradiation prevented the increase of interleukin (IL)-1ß, IL-6, IL-10, and cyclooxygenase-2 (COX-2), and induced an insignificant increase in collagen at 7 days after extraction, versus levels on day of extraction; no changes were found in the other parameters examined. Patients reported less pain at the site treated with superpulsed laser irradiation than at the control site. CONCLUSIONS: This study suggests that superpulsed laser irradiation may be a treatment of choice for patients scheduled for tooth extraction, as it provides clinical efficacy, is safe and well tolerated, and is able to prevent inflammation.


Asunto(s)
Terapia por Luz de Baja Intensidad , Extracción Dental , Cicatrización de Heridas/efectos de la radiación , Adolescente , Adulto , Análisis de Varianza , Colágeno/efectos de la radiación , Ciclooxigenasa 2/metabolismo , Femenino , Humanos , Interleucina-1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Estadísticas no Paramétricas , Resultado del Tratamiento
12.
JPEN J Parenter Enteral Nutr ; 35(1): 114-21, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21224438

RESUMEN

BACKGROUND: ω-3 polyunsaturated fatty acids (PUFAs) and ω-6 PUFAs have opposing influences on inflammation. The objective was to determine whether lipopolysaccharide (LPS)-induced cytokine release by human alveolar cells was affected by changes in the ω-3/ω-6 ratio of cell membranes induced by different supplies of PUFAs. METHODS: After LPS challenge, PUFAs were added to alveolar cells as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in 4 different DHA/AA ratios (1:1, 1:2, 1:4, and 1:7), and the effects on cytokine release were measured. RESULTS: The supply of 1:1 and 1:2 DHA/AA ratios reversed the baseline predominance of ω-6 over ω-3 in the ω-3/ω-6 PUFA ratio of cell membranes. The release of proinflammatory cytokines (tumor necrosis factor α, interleukin-6, and interleukin-8) was reduced by 1:1 and 1:2 DHA/AA ratios (P < .01 to P < .001) but increased by 1:4 and 1:7 DHA/AA ratios (P < .01 to P < .001) vs control. The 1:1 and 1:2 ratios increased the release of anti-inflammatory interleukin-10 (P < .001). The balance between proinflammatory and anti-inflammatory cytokines showed an anti-inflammatory response with 1:1 and 1:2 ratios and a proinflammatory response with 1:4 and 1:7 ratios (P < .001). CONCLUSIONS: This study showed that proinflammatory cytokine release was dependent on the proportion of ω-3 in the ω-3/ω-6 ratio of alveolar cell membranes, being reduced with the supply of a high proportion of DHA and increased with a high proportion of AA, respectively. These results support the biochemical basis for current recommendations to shift the PUFA supply from ω-6 to ω-3 in nutrition support of patients with acute lung injury.


Asunto(s)
Citocinas/biosíntesis , Ácidos Docosahexaenoicos/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Análisis de Varianza , Línea Celular , Membrana Celular/metabolismo , Células Epiteliales/metabolismo , Humanos , Inflamación/prevención & control , Interleucina-10/análisis , Interleucina-6/análisis , Interleucina-8/análisis , Lipopolisacáridos/farmacología , Modelos Teóricos , Alveolos Pulmonares/citología , Factor de Necrosis Tumoral alfa/análisis
13.
J Biomater Appl ; 25(6): 595-617, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20207775

RESUMEN

A 3D-glass-ceramic scaffold for bone tissue engineering with an interconnected macroporous network of pores was doped with silver ions in order to confer antibacterial properties. For this purpose, silver ions were selectively added to the scaffold surfaces through ion-exchange using an aqueous silver nitrate solution. The silver-doped scaffolds were characterized by means of leaching, in vitro antibacterial, and citotoxicity tests. In particular, the silver effect was examined through a broth dilution test in order to evaluate the proliferation of bacteria by counting the colonies forming units. Moreover, cytotoxicity tests were carried out to understand the effect of silver-containing scaffolds on cell adhesion, proliferation, and vitality. For all tests a comparison between silver-doped scaffold and silver-doped scaffold dry sterilized was performed.


Asunto(s)
Antiinfecciosos Locales/farmacología , Materiales Biocompatibles/farmacología , Trasplante Óseo/métodos , Cerámica/química , Vidrio/química , Nitrato de Plata/farmacología , Andamios del Tejido , Antiinfecciosos Locales/análisis , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Intercambio Iónico , Ensayo de Materiales/métodos , Microscopía Electrónica de Rastreo/métodos , Plata/farmacología , Nitrato de Plata/análisis , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Ingeniería de Tejidos/métodos , Difracción de Rayos X/métodos
14.
Cell Biochem Funct ; 28(7): 571-7, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20862655

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) mediate the effects of various ligands, known as peroxisome proliferators, a heterogeneous class of compounds including industrial chemicals, pharmaceuticals, and biomolecules such as fatty acids and eicosanoids. Among peroxisome proliferators, fibrate derivatives are considered specific ligands for PPARα, whereas eicosanoids, such as PGJ2, for PPARγ. The study aimed to clarify the relation between PPARs and apoptosis or proliferation on the same type of cells, using clofibrate as specific ligand of PPARα and PGJ2 as specific ligand of PPARγ. The cells used were human hepatocarcinoma HepG2 cells. The results showed that PPARα protein content increased in HepG2 cells treated with clofibrate, causing apoptosis in a time- and concentration-dependent way, as evidenced by the citofluorimetric assay and determination of BAD, myc and protein phosphatase 2A protein content. It also emerged that PPARγ increased in the same cells when treated with a specific ligand of this PPAR; in this case the increase of PPARγ did not cause an increase of apoptosis, but a time- and concentration-dependent inhibition of cell proliferation, evidenced by decreased cell numbers and increased number of cells in the G0/G1 phase of the cycle. It may be concluded that PPARα is chiefly related to apoptosis and PPARγ to cell proliferation.


Asunto(s)
Apoptosis , Proliferación Celular , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Clofibrato/farmacología , Células Hep G2 , Humanos , Ligandos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Concentración Osmolar , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacología , Proteína Fosfatasa 2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Proteína Letal Asociada a bcl/metabolismo
15.
J Trauma ; 68(6): 1439-44, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20234329

RESUMEN

BACKGROUND: Bone replacement is frequently needed in periodontal, orthopedic, and maxillofacial diseases. To avoid complications with autografts and allografts, artificial grafts (scaffolds) are candidates for stimulating bone regeneration after colonization with osteoblasts. Moreover, osteoblast activity can be induced by biological or physical stimulation. In this research, extracorporeal shock waves were used to improve the ability of human osteoblasts to colonize scaffolds and to induce their osteogenic properties. METHODS: Osteoblasts, treated with shock waves, were seeded on glass-ceramic macroporous scaffolds. Cells in scaffolds were counted after detachment and examined for calcium nodule formation (Alizarin staining), for differentiation markers (real time polymerase chain reaction), and for scaffold colonization (scanning electron microscope). RESULTS: Shock waves initially increased both the number and the activity of osteoblasts in the scaffold, but subsequently increased only osteoblast activity. Moreover, shock waves favored scaffold colonization even in the deeper layers. CONCLUSIONS: The calcium deposits and differentiation markers studied have demonstrated that shock waves increase osteoblast migration and penetration into scaffolds. CLINICAL RELEVANCE: This study may provide an important starting point for the introduction of shock waves to boost bone formation through osteoblast stimulation in diseases characterized by bone defects.


Asunto(s)
Ondas de Choque de Alta Energía , Osteoblastos/fisiología , Andamios del Tejido , Análisis de Varianza , Regeneración Ósea/fisiología , Línea Celular , Cerámica/química , Vidrio/química , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Poliuretanos/química , Porosidad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
J Clin Periodontol ; 35(6): 532-8, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18384390

RESUMEN

AIMS: The aim of this split-mouth study was to investigate levels of tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta2) and interleukin-1 beta (IL-1beta) in gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PICF) after a 21-day-period of de novo plaque accumulation in the same patient. MATERIAL AND METHODS: In 25 patients, samples of GCF and PICF were collected in the sulcus of the tooth and of the implant after professional hygiene. After the no-hygiene phase (21 days), second samples of GCF and PICF were taken. Third samples were collected after 69 days of re-establishment oral hygiene techniques. The crevicular fluids were used to determine the volume and the levels of TNF-alpha, TGF-beta2 and IL-1beta. RESULTS: The volume of the crevicular fluids increased significantly after 21 days of plaque accumulation around teeth and implants and decreased significantly by 69 days. TNF-alpha and TGF-beta2 did not change significantly among the three different samples. A significant increase of IL-1beta was observed after plaque accumulation around the teeth GCF, whereas in the PICF the increase was not statistically significant. CONCLUSIONS: These data suggest that increased volumes of GCF and PICF could be useful markers of early inflammation in gingival and peri-implant tissues. In the presence of de novo plaque, implants showed lower, and nearly significant, levels of IL-1beta compared with teeth.


Asunto(s)
Citocinas/biosíntesis , Implantes Dentales , Placa Dental/inmunología , Líquido del Surco Gingival/inmunología , Gingivitis/inmunología , Adulto , Anciano , Placa Dental/terapia , Femenino , Gingivitis/metabolismo , Humanos , Interleucina-1beta/biosíntesis , Masculino , Persona de Mediana Edad , Higiene Bucal , Índice Periodontal , Recurrencia , Estadísticas no Paramétricas , Factor de Crecimiento Transformador beta2/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis
17.
Br J Nutr ; 100(4): 739-50, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18304389

RESUMEN

Epidemiological studies suggest that dietary PUFA may influence breast cancer progression. n-3 PUFA are generally known to exert antitumour effects, whereas reports relative to n-6 PUFA anti-carcinogen effects are controversial. Arachidonic acid (AA; 20:4n-6) and its metabolites have been shown to inhibit the growth of human breast cancer cell lines, even if the downstream mechanisms by which AA may influence carcinogenesis remain unresolved. We explored the molecular basis for AA influence on proliferation, signal transduction and apoptosis in two human breast cancer cell lines, MCF-7 and MDA-MB-231. In both cell lines AA inhibited cell growth in a dose-dependent manner, even if MDA-MB-231 was somewhat more growth-inhibited than MCF-7. AA decreased extracellular signal-regulated protein kinase 1/2 phosphorylation level, and positively modulated PPARgamma and PPARalpha expression, with only a slight effect against PPARbeta/delta. In addition, AA increased Bak (an apoptosis-regulating protein) expression and reduced procaspase-3 and -9 levels only in MDA-MB-231 cells, thus indicating that the growth inhibitory effect can be correlated with apoptosis induction. In both cell lines the use of a specific antagonist made it possible to establish a relationship between AA growth inhibitory effect and PPARalpha involvement. AA decreases cell proliferation most likely by inducing apoptosis in MDA-MB-231 cells, while in the MCF-7 cell line the growth inhibitory activity can be attributed to the inhibition of the signal transduction pathway involved in cell proliferation. In both cases, the results here presented suggest PPARalpha as a possible contributor to the growth inhibitory effect of AA.


Asunto(s)
Ácido Araquidónico/farmacología , Neoplasias de la Mama/patología , PPAR alfa/farmacología , Análisis de Varianza , Apoptosis/efectos de los fármacos , Western Blotting/métodos , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Fosforilación/efectos de los fármacos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos
18.
Int J Cancer ; 121(11): 2395-401, 2007 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-17691108

RESUMEN

Conjugated linoleic acid (CLA), found in dairy products, in beef and lamb has been demonstrated to possess anticancer properties protecting several tissues from developing cancer. Moreover, it has been shown to modulate apoptosis in several cancer cell lines. The aim of this study was to investigate which signaling transduction pathways were modulated in CLA-induced apoptosis in human hepatoma SK-HEP-1 cells. The cells exposed to CLA were evaluated for PPARalpha, PP2A, pro-apoptotic proteins Bak, Bad and caspases, and anti-apoptotic proteins Bcl-2 and Bcl-X(L). Cells were also treated with okadaic acid, a PP2A inhibitor, or with Wy-14643, a specific PPARalpha agonist. The CLA-induced apoptosis was concomitant to the increase of percentage of cells in the S phase, PPARalpha, PP2A and pro-apoptotic proteins; simultaneously, antiapoptotic proteins decreased. Inhibition of PP2A prevented apoptosis, and PPARalpha agonist showed similar effect as CLA. The increased PP2A could be responsible for the dephosphorylation of Bcl-2 and Bad, permitting apoptotic activity of Bax and Bad. The increase of caspase 8 and 9 suggested that both the intrinsic and extrinsic apoptotic pathways were induced. PP2A was probably increased by PPARalpha, since putative PPRE sequences were found in genes encoding its subunits. In conclusion, CLA induces apoptosis in human hepatoma SK-HEP-1 cells, by increasing PPARalpha, PP2A and pro-apoptotic proteins.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Ácido Linoleico/farmacología , Neoplasias Hepáticas/metabolismo , PPAR alfa/metabolismo , Proteína Fosfatasa 2/metabolismo , Transducción de Señal/efectos de los fármacos , Secuencia de Bases , Western Blotting , Caspasas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , ADN de Neoplasias/efectos de los fármacos , Humanos , Datos de Secuencia Molecular , Ácido Ocadaico/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Pirimidinas/farmacología , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Proteína Letal Asociada a bcl/metabolismo , Proteína bcl-X/metabolismo
19.
Br J Nutr ; 96(1): 22-7, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16869987

RESUMEN

Conjugated linoleic acid (CLA) has protective properties in breast cancer. Here, we studied the mechanisms underlying the effects of CLA on MCF-7 breast cancer cell proliferation, especially in correlation with the involvement of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and protein phosphatase 2A (PP2A). CLA inhibits MCF-7 cell growth in a concentration- and time-dependent manner, without triggering apoptosis. In assessing expression levels of proteins that play obligatory roles in the ERK cascade, we evidenced that CLA down-regulated Raf-1 and decreased levels of phospho-ERK1/2, as well as c-myc expression. Increase in PP2A expression rates were additionally observed after CLA treatment of MCF-7 cells. The above effects, as well as CLA-induced inhibition of cell growth, were reversed by okadaic acid, a specific inhibitor of PP2A. Thus, PP2A likely participates in deactivation of ERK1/2, and its up-regulation may represent a novel mechanism for CLA-induced inhibition of cell proliferation.


Asunto(s)
Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ácidos Linoleicos Conjugados/farmacología , Fosfoproteínas Fosfatasas/metabolismo , Neoplasias de la Mama/prevención & control , Carcinógenos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Medios de Cultivo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Ácidos Linoleicos Conjugados/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Ácido Ocadaico/farmacología , Proteína Fosfatasa 2 , Regulación hacia Arriba/fisiología
20.
J Toxicol Environ Health A ; 69(5): 353-65, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16455614

RESUMEN

Phthalate esters are a widely used class of water-insoluble organic chemicals. The adverse effects of di(2-ethylhexyl) phthalate (DEHP) were chiefly studied in animals, while their potential toxicity to humans has not been properly evaluated. It was hypothesized that the effect of DEHP on human cells depends on the concentration, and this study examined the effects of different concentrations of DEHP on cell growth in cultured human keratinocytes NCTC 2544, together with the possible involvement of peroxisome proliferator-activated receptors (PPARs) in mediating the effects. After exposure to DEHP, the number of NCTC 2544 cells in the monolayer decreased in a concentration-dependent and time-dependent manner, whereas the cells that were detached from the monolayer increased, and died via necrosis. The decrease of cell growth was confirmed by the inhibition of pErk1, pErk2, and changes in the c-myc protein content. With regard to PPARs, the PPARbeta protein content increased, whereas PPARalpha decreased. To demonstrate the involvement of PPARbeta in inhibiting cell growth, the use of an antisense oligonucleotide against this receptor revealed the prevention of DEHP-induced cell growth inhibition. In addition, the treatment of keratinocytes with a specific ligand of PPARbeta (L165041) showed a concentration-dependent inhibition of cell growth, as with DEHP. In conclusion, the effect of DEHP on human keratinocytes is concentration dependent, and this effect is mediated via PPARs.


Asunto(s)
Dietilhexil Ftalato/farmacología , Queratinocitos/efectos de los fármacos , Oligonucleótidos Antisentido/farmacología , Receptores Activados del Proliferador del Peroxisoma/efectos de los fármacos , Proliferadores de Peroxisomas/farmacología , Plastificantes/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Queratinocitos/enzimología , L-Lactato Deshidrogenasa/metabolismo , Ratas
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