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1.
Chemosphere ; 353: 141429, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38364917

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) comprise a group of compounds resulting from the incomplete combustion of organic matter. Firefighters engaged in fire suppression are highly exposed to PAHs. This study centered on evaluating the exposure levels and health risks of PAHs in South Korean firefighters involved in firefighting activities. The concentrations of 10 PAH metabolites in the urine of firefighters were measured immediately after, and two weeks post their engagement in extinguishing a large tire factory fire. The levels of OH-PAHs in urine samples immediately after fire suppression were elevated by a factor of 1.01-1.84 compared to urine samples from non-exposed period. The median concentration of total PAH metabolites (OH-PAHs) was higher in urine samples immediately after fire suppression (5910 ng/g creatinine) than in urine samples from non-exposed periods (5020 ng/g creatinine). However, the ∑OH-PAH levels in firefighters' urine were related to personal habits such as smoking. The concentrations of all individual OH-PAHs in the urine samples of nonsmokers exhibited a substantial increase, ranging from 1.37 to 2.3 times, clearly demonstrating that firefighting activities were a substantial source of PAH exposure. The calculated values associated with the health risks stemming from exposure to PAHs, including carcinogenic risk, total estimated daily intake (TEDI), and hazard quotients/index (HQs/HI), all fell within acceptable limits, indicating negligible risk. However, the HQ/HI values and TEDI for individual and total PAH exposures, except those for naphthalene, were 1.36-2.00 times higher in firefighters' samples taken after firefighting operations compared to those during regular duty. This underscores the need for more comprehensive investigations to comprehend the singular impact of firefighting activities due to the diverse sources of PAH emissions in the environment.


Asunto(s)
Contaminantes Ocupacionales del Aire , Bomberos , Exposición Profesional , Hidrocarburos Policíclicos Aromáticos , Humanos , Contaminantes Ocupacionales del Aire/análisis , Exposición Profesional/análisis , Creatinina , Monitoreo del Ambiente/métodos , Hidrocarburos Policíclicos Aromáticos/análisis
2.
Neuro Oncol ; 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38085571

RESUMEN

BACKGROUND: Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explores 11C-acetate PET as an imaging technique for detecting reactive astrogliosis. METHODS: Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated 11C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and MCT1 expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of 11C-acetate uptake beyond MRI and prognosis. RESULTS: Elevated 11C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of 11C-acetate uptake beyond contrast-enhanced MRI was associated with worse prognosis. CONCLUSION: Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of 11C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.

4.
Front Microbiol ; 13: 1014872, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36212836

RESUMEN

Leuconostoc species are important microorganisms in food fermentation but also cause food spoilage. Although these species are commercially important, their taxonomy is still based on inaccurate identification methods. Here, we used computational pangenome analysis to develop a real-time PCR-based method for identifying and differentiating the 12 major Leuconostoc species found in food. Analysis of pan and core-genome phylogenies showed clustering of strains into 12 distinct groups according to the species. Pangenome analysis of 130 Leuconostoc genomes from these 12 species enabled the identification of each species-specific gene. In silico testing of the species-specific genes against 143 publicly available Leuconostoc and 100 other lactic acid bacterial genomes showed that all the assays had 100% inclusivity/exclusivity. We also verified the specificity for each primer pair targeting each specific gene using 23 target and 124 non-target strains and found high specificity (100%). The sensitivity of the real-time PCR method was 102 colony forming units (CFUs)/ml in pure culture and spiked food samples. All standard curves showed good linear correlations, with an R 2 value of ≥0.996, suggesting that screened targets have good specificity and strong anti-interference ability from food sample matrices and non-target strains. The real-time PCR method can be potentially used to determine the taxonomic status and identify the Leuconostoc species in foods.

5.
Sci Adv ; 8(15): eabn1646, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35427152

RESUMEN

Wound healing is the dynamic tissue regeneration process replacing devitalized and missing tissue layers. With the development of photomedicine techniques in wound healing, safe and noninvasive photobiomodulation therapy is receiving attention. Effective wound management in photobiomodulation is challenged, however, by limited control of the geometrical mismatches on the injured skin surface. Here, adhesive hyaluronic acid-based gelatin nanofibrous membranes integrated with multiple light-emitting diode (LED) arrays are developed as a skin-attachable patch. The nanofibrous wound dressing is expected to mimic the three-dimensional structure of the extracellular matrix, and its adhesiveness allows tight coupling between the wound sites and the flexible LED patch. Experimental results demonstrate that our medical device accelerates the initial wound healing process by the synergetic effects of the wound dressing and LED irradiation. Our proposed technology promises progress for wound healing management and other biomedical applications.

6.
Adv Exp Med Biol ; 1351: 125-148, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35175615

RESUMEN

Graphene is sp2-hybridized carbon structure-based two-dimensional (2D) sheet. Graphene-based nanomaterials possess several features such as unique mechanical, electronic, thermal, and optical properties, high specific surface area, versatile surface functionalization, and biocompatibility, which attracted researcher's interests in various fields including biomedicine. In this chapter, we particularly focused on the biomedical imaging applications of graphene-based nanomaterials like graphene oxide (GO), reduced graphene oxide (rGO), graphene quantum dots (GQDs), graphene oxide quantum dots (GOQDs), and other derivatives, which utilize their outstanding optical properties. There are some biomedical imaging modalities using Graphene-based Nanomaterials, among which we will highlight fluorescence imaging, Raman imaging, magnetic resonance imaging, and photoacoustic imaging. We also discussed the brief perspectives and future application related to them.


Asunto(s)
Grafito , Nanoestructuras , Puntos Cuánticos , Imagen Óptica
7.
Front Med (Lausanne) ; 9: 970546, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36590955

RESUMEN

Background: Mechanical stress are one of the pathogenesis of axial spondyloarthritis (axSpA). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. We aimed to investigate whether pregnancy affects radiographic progression in patients with radiographic axSpA (r-axSpA) based on computed tomography (CT) evaluations. Materials and methods: This retrospective study included women with r-axSpA aged 19-49 years who underwent at least two CT evaluations of the whole spine and/or sacroiliac joints (SIJs) at intervals of 2-4 years. To compare radiographic progression after delivery, we classified the patients into two groups: delivery group and controls. The delivery group was restricted to women who had the first CT ∼2 years before delivery and the second CT ∼2 years after delivery. The CT Syndesmophyte Score (CTSS) (0-522) and SIJ scores (0-40) were used to evaluate spinal syndesmophytes and erosion, joint space narrowing, and sclerosis of the SIJs. Results: A total of 21 women in the delivery group and 38 women in the control group were included. The median (Q1-Q3) CTSS at baseline in the delivery group and controls was 19 (16-23) and 20 (13.25-27.75), and the median progression was 1 (0-3) and 0 (0-1) during the median 2.9-year follow-up, respectively. The median (Q1-Q3) SIJ score at baseline in the delivery group and controls was 13 (8-22) and 11 (6-22), and the median progression was 1.5 (0-3) and 1 (0-2), respectively. Using cut-off 0.5, 52.9, and 61.9% of r-axSpA patients and 39.3 and 44.4% of controls showed progression of whole spine and SIJs, respectively. However, no difference in proportion of spinal and SIJ progression and absolute score changes per time point was observed between two groups. Moreover, the SIJ score changes were comparable according to the delivery method. Conclusion: Pregnancy and delivery do not affect the radiographic progression of the spine and SIJs in women with r-axSpA assessed by CT.

8.
BMC Biotechnol ; 21(1): 52, 2021 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-34482828

RESUMEN

BACKGROUND: Equine chorionic gonadotropin (eCG), which comprises highly glycosylated α-subunit and ß-subunit, is a unique member of the glycoprotein hormone family as it elicits both follicle-stimulating hormone (FSH)-like and luteinizing hormone (LH)-like responses in non-equid species. To examine the biological function of glycosylated sites in eCG, the following glycosylation site mutants were constructed: eCGß/αΔ56, substitution of Asn56 of α-subunit with Gln; eCGß-D/α, deletion of the O-linked glycosylation site at the carboxyl-terminal peptide (CTP) region of the ß-subunit; eCGß-D/αΔ56, double mutant. The recombinant eCG (rec-eCG) mutants were expressed in Chinese hamster ovary suspension (CHO-S) cells. The FSH-like and LH-like activities of the mutants were examined using CHO-K1 cells expressing rat lutropin/CG receptor (rLH/CGR) and rat FSH receptor (rFSHR). RESULTS: Both rec-eCGß/α and rec-eCGß/αΔ56 were efficiently secreted into the CHO-S cell culture medium on day 1 post-transfection. However, the secretion of eCGß-D/α and eCGß-D/αΔ56, which lack approximately 12 O-linked glycosylation sites, was slightly delayed. The expression levels of all mutants were similar (200-250 mIU/mL) from days 3 to 7 post-transfection. The molecular weight of rec-eCGß/α, rec-eCGß/αΔ56 and rec-eCG ß-D/α were in the ranges of 40-45, 37-42, and 34-36 kDa, respectively. Treatment with peptide-N-glycanase F markedly decreased the molecular weight to approximately 5-10 kDa. Rec-eCGß/αΔ56 exhibited markedly downregulated LH-like activity. The signal transduction activity of both double mutants was completely impaired. This indicated that the glycosylation site at Asn56 of the α-subunit plays a pivotal role in the LH-like activity of eCG. Similarly, the FSH-like activity of the mutants was markedly downregulated. eCGß-D/α exhibited markedly downregulated LH-like and FSH-like activities. CONCLUSIONS: Rec-eCGß/α exhibits potent biological activity in cells expressing rLH/CGR and rFSHR. The findings of this study suggest that the LH-like and FSH-like activities of eCG are regulated by the N-linked glycosylation site at Asn56 of the eCG α-subunit and/or by the O-linked glycosylation sites of the eCG ß-subunit. These findings improved our understanding of the mechanisms underlying both LH-like and FSH-like activities of eCG.


Asunto(s)
Gonadotropina Coriónica , Hormona Luteinizante , Animales , Células CHO , Gonadotropina Coriónica/metabolismo , Cricetinae , Cricetulus , Glicosilación , Caballos , Hormona Luteinizante/metabolismo , Ratas , Receptores de HFE/metabolismo , Receptores de HL/genética , Receptores de HL/metabolismo , Transducción de Señal
9.
PLoS One ; 16(4): e0249578, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33861786

RESUMEN

INTRODUCTION AND OBJECTIVE: Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction. METHODS: Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed. RESULTS: A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05). CONCLUSION: Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.


Asunto(s)
Densidad Ósea , Enfermedades Óseas Metabólicas/patología , Placa de Crecimiento/patología , Vértebras Lumbares/patología , Fracturas de la Columna Vertebral/patología , Espondilitis Anquilosante/complicaciones , Tomografía Computarizada por Rayos X/métodos , Adulto , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/etiología , Placa de Crecimiento/diagnóstico por imagen , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen
10.
BMC Biotechnol ; 20(1): 59, 2020 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-33176770

RESUMEN

BACKGROUND: Equine chorionic gonadotropin (eCG) induces super-ovulation in laboratory animals. Notwithstanding its extensive usage, limited information is available regarding the differences between the in vivo effects of natural eCG (N-eCG) and recombinant eCG (R-eCG). This study aimed to investigate the gene expression profiles of mouse ovaries upon stimulation with N-eCG and R-eCG produced from CHO-suspension (CHO-S) cells. R-eCG gene was constructed and transfected into CHO-S cells and quantified. Subsequently, we determined the metabolic clearance rate (MCR) of N-eCG and R-eCG up to 24 h after intravenous administration through the mice tail vein and identified differentially expressed genes in both ovarian tissues, via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). RESULTS: R-eCG was markedly expressed initially after transfection and maintained until recovery on day 9. Glycan chains were substantially modified in R-eCG protein produced from CHO-S cells and eliminated through PNGase F treatment. The MCR was higher for R-eCG than for N-eCG, and no significant difference was observed after 60 min. Notwithstanding their low concentrations, R-eCG and N-eCG were detected in the blood at 24 h post-injection. Microarray analysis of ovarian tissue revealed that 20 of 12,816 genes assessed therein were significantly up-regulated and 43 genes were down-regulated by > 2-fold in the group that received R-eCG (63 [0.49%] differentially regulated genes in total). The microarray results were concurrent with and hence validated by those of RT-PCR, qRT-PCR, and IHC analyses. CONCLUSIONS: The present results indicate that R-eCG can be adequately produced through a cell-based expression system through post-translational modification of eCG and can induce ovulation in vivo. These results provide novel insights into the molecular mechanisms underlying the up- or down-regulation of specific ovarian genes and the production of R-eCG with enhanced biological activity in vivo.


Asunto(s)
Gonadotropina Coriónica/metabolismo , Perfilación de la Expresión Génica , Ovario/metabolismo , Proteínas Recombinantes/metabolismo , Animales , Gonadotropina Coriónica/farmacología , Femenino , Gonadotropinas Equinas/administración & dosificación , Gonadotropinas Equinas/metabolismo , Caballos , Inmunohistoquímica , Masculino , Ratones , Análisis por Micromatrices , Ovulación/efectos de los fármacos , Ovulación/metabolismo
11.
Arch Plast Surg ; 47(4): 310-316, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32718109

RESUMEN

BACKGROUND: To produce patient-specific nasal implants, it is necessary to harvest and grow autologous cartilage. It is crucial to the proliferation and growth of these cells for scaffolds similar to the extracellular matrix to be prepared. The pore size of the scaffold is critical to cell growth and interaction. Thus, the goal of this study was to determine the optimal pore size for the growth of chondrocytes and fibroblasts. METHODS: Porous disc-shaped scaffolds with 100-, 200-, 300-, and 400-µm pores were produced using polycaprolactone (PCL). Chondrocytes and fibroblasts were cultured after seeding the scaffolds with these cells, and morphologic evaluation was performed on days 2, 14, 28, and 56 after cell seeding. On each of those days, the number of viable cells was evaluated quantitatively using an MTT assay. RESULTS: The number of cells had moderately increased by day 28. This increase was noteworthy for the 300- and 400-µm pore sizes for fibroblasts; otherwise, no remarkable difference was observed at any size except the 100-µm pore size for chondrocytes. By day 56, the number of cells was observed to increase with pore size, and the number of chondrocytes had markedly increased at the 400-µm pore size. The findings of the morphologic evaluation were consistent with those of the quantitative evaluation. CONCLUSIONS: Experiments using disc-type PCL scaffolds showed (via both morphologic and quantitative analysis) that chondrocytes and fibroblasts proliferated most extensively at the 400-µm pore size in 56 days of culture.

12.
Pharmaceutics ; 12(8)2020 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-32722426

RESUMEN

Research on cancer theragnosis with gold nanoparticles (AuNPs) has rapidly increased, as AuNPs have many useful characteristics for various biomedical applications, such as biocompatibility, tunable optical properties, enhanced permeability and retention (EPR), localized surface plasmon resonance (LSPR), photothermal properties, and surface enhanced Raman scattering (SERS). AuNPs have been widely utilized in cancer theragnosis, including phototherapy and photoimaging, owing to their enhanced solubility, stability, biofunctionality, cancer targetability, and biocompatibility. In this review, specific characteristics and recent modifications of AuNPs over the past decade are discussed, as well as their application in cancer theragnostics and future perspectives. In the future, AuNP-based cancer theragnosis is expected to facilitate the development of innovative and novel strategies for cancer therapy.

13.
Cancers (Basel) ; 12(4)2020 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-32290285

RESUMEN

Hyaluronic acid (HA) is a natural mucopolysaccharide and has many useful advantages, including biocompatibility, non-immunogenicity, chemical versatility, non-toxicity, biodegradability, and high hydrophilicity. Numerous tumor cells overexpress several receptors that have a high binding affinity for HA, while these receptors are poorly expressed in normal body cells. HA-based drug delivery carriers can offer improved solubility and stability of anticancer drugs in biological environments and allow for the targeting of cancer treatments. Based on these benefits, HA has been widely investigated as a promising material for developing the advanced clinical cancer therapies in various formulations, including nanoparticles, micelles, liposomes, and hydrogels, combined with other materials. We describe various approaches and findings showing the feasibility of improvement in theragnosis probes through the application of HA.

14.
Biomater Res ; 23: 16, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31695925

RESUMEN

BACKGROUND: Alopecia has become a very common disease that many people around the world are suffered. Minoxidil (MXD) is the most well-known commercialized drug in its treatment. However, in the case of MXD administration, there are some problems with low efficiency of transdermal delivery and additional side effects. METHOD: MXD and Rhodamine B (Rho B) are encapsulated in poly(Lactide-co-Glycolide) grafted hyaluronate nanoparticles (HA-PLGA/MXD NPs, HA-PLGA/Rho B NPs) which is prepared with W/O/W solvent evaporation method. After then, the investigation is carried out to confirm the feasibility of NPs in alopecia treatment. RESULTS: Both of HA-PLGA/MXD NPs and HA-PLGA/Rho B NPs are successfully prepared. In addition, it is confirmed that HA-PLGA NPs sufficiently delivered to cells without any significant cytotoxicity by cell viability, cellular uptake and skin permeation test. CONCLUSION: Taken together, HA-PLGA NPs as a transdermal delivery carrier to hair follicle cells can be exploited to develop the efficient and effective platform of transdermal drug delivery for the treatment of various diseases.

15.
ACS Appl Mater Interfaces ; 10(48): 41655-41663, 2018 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-30404444

RESUMEN

Plasmon-enhanced particle trapping was demonstrated using a hybrid structure of nanoparticles and nanorods. In order to intensify localized surface plasmon resonance (LSPR), gold nanoparticles (AuNPs) were deposited on zinc oxide nanorods (ZnONRs). The synergistic effect caused by the hybrid structure was identified experimentally. Numerical analysis revealed that the LSPR-induced photophysical processes such as plasmonic heating and near-field enhancement were improved by the existence of ZnONRs. The role of the ZnONR in enhancing the particle-trapping velocity was explored by examining the scattered electric field, Poynting vector, and temperature gradient over the nanostructures calculated from the simulation. It was found that polystyrene microparticles and Escherichia coli cells were successfully trapped by using the ZnONR/AuNP plasmonic structure. A relatively high dielectric constant and nanorod geometry of ZnO enabled the hybrid substrate to enhance trapping performance, compared with a control case fabricated using only gold nanoislands.

16.
Dev Reprod ; 22(1): 55-64, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29707684

RESUMEN

Previous studies showed that recombinant equine chorionic gonadotropin (rec-eCGß/α) exhibits both follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-like activities in rat LHR- and FSHR-expressing cells. In this study, we analyzed signal transduction by eelFSHR and eelLHR upon stimulation with rec-eCGß/α and native eCG. The cyclic adenosine monophosphate (cAMP) stimulation in CHO-K1 cells expressing eelLHR was determined upon exposure to different doses (0-1,450 ng/mL) of rec-eCGß/α and native eCG. The EC50 values of rec-eCGß/α and native eCG were 172.4 and 786.6 ng/mL, respectively. The activity of rec-eCGß/α was higher than that of native eCG. However, signal transduction in the CHO PathHunter Parental cells expressing eelFSHR was not enhanced by stimulation with both agonist rec-eCGß/α and native eCG. We concluded that rec-eCGß/α and native eCG were completely active in cells expressing eelLHR, similar to the activity in the mammalian cells expressing LHRs. However, rec-eCGß/α and native eCG did not invoke any signaling response in the cells expressing eelFSHR. These results suggest that eCG has a potent activity in cells expressing eelLHR. Thus, we also suggest that rec-eCGß/α can induce eel maturation by administering gonadotropic reagents (LH), such as salmon pituitary extract.

17.
PLoS One ; 11(12): e0167713, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28030574

RESUMEN

Periodontitis is a very common oral inflammatory disease that results in the destruction of supporting connective and osseous tissues of the teeth. Although the exact etiology is still unclear, Gram-negative bacteria, especially Porphyromonas gingivalis in subgingival pockets are thought to be one of the major etiologic agents of periodontitis. Endothelin (ET) is a family of three 21-amino acid peptides, ET-1, -2, and -3, that activate G protein-coupled receptors, ETA and ETB. Endothelin is involved in the occurrence and progression of various inflammatory diseases. Previous reports have shown that ET-1 and its receptors, ETA and ETB are expressed in the periodontal tissues and, that ET-1 levels in gingival crevicular fluid are increased in periodontitis patients. Moreover, P. gingivalis infection has been shown to induce the production of ET-1 along with other inflammatory cytokines. Despite these studies, however, the functional significance of endothelin in periodontitis is still largely unknown. In this study, we explored the cellular and molecular mechanisms of ET-1 action in periodontitis using human gingival epithelial cells (HGECs). ET-1 and ETA, but not ETB, were abundantly expressed in HGECs. Stimulation of HGECs with P. gingivalis or P. gingivalis lipopolysaccharide increased the expression of ET-1 and ETA suggesting the activation of the endothelin signaling pathway. Production of inflammatory cytokines, IL-1ß, TNFα, and IL-6, was significantly enhanced by exogenous ET-1 treatment, and this effect depended on the mitogen-activated protein kinases via intracellular Ca2+ increase, which resulted from the activation of the phospholipase C/inositol 1,4,5-trisphosphate pathway. The inhibition of the endothelin receptor-mediated signaling pathway with the dual receptor inhibitor, bosentan, partially ameliorated alveolar bone loss and immune cell infiltration. These results suggest that endothelin plays an important role in P. gingivalis-mediated periodontitis. Thus, endothelin antagonism may be a potential therapeutic approach for periodontitis treatment.


Asunto(s)
Citocinas/metabolismo , Endotelina-1/metabolismo , Porphyromonas gingivalis/fisiología , Animales , Calcio/metabolismo , Progresión de la Enfermedad , Endotelina-1/biosíntesis , Células Epiteliales/citología , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Humanos , Inflamación/metabolismo , Masculino , Ratones , Periodontitis/patología , Transducción de Señal
18.
Nucl Med Biol ; 42(7): 621-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25899941

RESUMEN

INTRODUCTION: In vivo tracking of the transplanted stem cells is important in pre-clinical research of stem cell therapy for myocardial infarction. We examined the feasibility of adenovirus-mediated sodium iodide symporter (NIS) gene to cell tracking imaging of transplanted stem cells in a canine infarcted myocardium by clinical single photon emission computed tomography (SPECT). METHODS: Beagle dogs were injected intramyocardially with NIS-expressing adenovirus-transfected canine stem cells (Ad-hNIS-canine ADSCs) a week after myocardial infarction (MI) development. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) and (99m)Tc-pertechnetate ((99m)TcO4(-)) SPECT imaging were performed for assessment of infarcted myocardium and viable stem cell tracking. Transthoracic echocardiography was performed to monitor any functional cardiac changes. RESULTS: Left ventricular ejection fraction (LVEF) was decreased after LAD ligation. There was no significant difference in EF between the groups with the stem cell or saline injection. (125)I uptake was higher in Ad-hNIS-canine ADSCs than in non-transfected ADSCs. Cell proliferation and differentiation were not affected by hNIS-carrying adenovirus transfection. (99m)Tc-MIBI myocardial SPECT imaging showed decreased radiotracer uptake in the infarcted apex and mid-anterolateral regions. Ad-hNIS-canine ADSCs were identified as a region of focally increased (99m)TcO4(-) uptake at the lateral wall and around the apex of the left ventricle, peaked at 2 days and was observed until day 9. CONCLUSIONS: Combination of adenovirus-mediated NIS gene transfection and clinical nuclear imaging modalities enables to trace the fate of transplanted stem cells in infarcted myocardium for translational in vivo cell tracking study for prolonged duration.


Asunto(s)
Rastreo Celular/métodos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/terapia , Células Madre/diagnóstico por imagen , Células Madre/metabolismo , Simportadores/metabolismo , Adenoviridae/genética , Adipocitos/diagnóstico por imagen , Adipocitos/metabolismo , Adipocitos/patología , Animales , Diferenciación Celular , Perros , Femenino , Infarto del Miocardio/patología , Trasplante de Células Madre/métodos , Células Madre/patología , Simportadores/genética , Tomografía Computarizada de Emisión de Fotón Único/métodos , Transfección/métodos , Resultado del Tratamiento
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