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The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.
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AIM: The main aim of this study was to compare the long-term outcome of a conventional colorectal endoscopic submucosal dissection (ESD) in which submucosal dissection was continued throughout until the completion of resection (ESD-T) to hybrid endoscopic submucosal dissection (ESD-H) in the colorectum. METHOD: Medical records of 836 colorectal neoplasia patients treated by ESD-T or ESD-H were reviewed. ESD-H was defined as colorectal ESD with additional snaring in the final stage of the procedure. Primary outcomes were the overall and metastatic recurrence rates. Secondary outcomes were short-term outcomes such as the en bloc resection rate, procedure time and adverse events. RESULTS: The overall recurrence rate was higher in the ESD-H than in the ESD-T group (5.7% vs 0.7%, P = 0.001). The metastatic recurrence rate showed no significant difference between these groups (1.4% vs 1.4%, P = 1.000). Multivariate analysis revealed that a failed en bloc resection (hazard ratio 24.097; 95% CI 5.446-106.237; P < 0.001) and larger tumour size (hazard ratio 1.042; 95% CI 1.014-1.070; P = 0.003) were independently associated with overall recurrence. The ESD-H group showed a lower en bloc resection rate (56.8% vs 96.5%, P < 0.001), shorter procedure time (45.6 vs 54.3 min, P < 0.001) and higher perforation rate (10.3% vs 6.0%, P = 0.029). CONCLUSION: Although long-term outcomes in terms of overall recurrence are inferior following ESD-H, a failed en bloc resection and large tumour size are the only independent risk factors for recurrence. Further investigations are warranted to improve the long-term outcomes of ESD-H.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Neoplasias Colorrectales/cirugía , Disección , Resección Endoscópica de la Mucosa/efectos adversos , Humanos , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB), a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti) implants using poly(lactic-co-glycolic acid) (PLGA) coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.
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Regeneración Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/fisiopatología , Gentisatos/farmacología , Osteoporosis/fisiopatología , Impresión Tridimensional , Prótesis e Implantes , Animales , Densidad Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Modelos Animales de Enfermedad , Femenino , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Fémur/patología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/diagnóstico por imagen , Osteoporosis/patología , Ovariectomía , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Titanio/farmacología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
High-grade gliomas (HGG), including glioblastomas, are characterized by invasive growth, resistance to therapy, and high inter- and intra-tumoral heterogeneity. The key histological hallmarks of glioblastoma are pseudopalisading necrosis and microvascular proliferation, which allow pathologists to distinguish glioblastoma from lower-grade gliomas. In addition to being genetically and molecularly heterogeneous, HGG are also heterogeneous with respect to the composition of their microenvironment. The question of whether this microenvironmental heterogeneity is driven by the molecular identity of the tumor remains controversial. However, this question is of utmost importance since microenvironmental, non-neoplastic cells are key components of the most radiotherapy- and chemotherapy-resistant niches of the tumor. Our work demonstrates a versatile, reliable, and reproducible adult HGG mouse model with NF1-silencing as a driver mutation. This model shows significant differences in tumor microenvironment, expression of subtype-specific markers, and response to standard therapy when compared to our established PDGFB-overexpressing HGG mouse model. PDGFB-overexpressing and NF1-silenced murine tumors closely cluster with human proneural and mesenchymal subtypes, as well as PDGFRA-amplified and NF1-deleted/mutant human tumors, respectively, at both the RNA and protein expression levels. These models can be generated in fully immunocompetent mixed or C57BL/6 genetic background mice, and therefore can easily be incorporated into preclinical studies for cancer cell-specific or immune cell-targeting drug discovery studies.
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Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica/genética , Glioma/patología , Mutación/genética , Proteínas Proto-Oncogénicas c-sis/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Línea Celular Tumoral , Proliferación Celular , Ventrículos Cerebrales/patología , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/terapia , Humanos , Receptores de Hialuranos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/metabolismo , Nestina/genética , Nestina/metabolismo , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Neuropéptidos/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , TemozolomidaRESUMEN
BACKGROUND AND OBJECTIVE: The predictability of conventional periodontal treatments for damaged periodontal tissue is limited, particularly on the regeneration of new cementum. As signaling molecules, a range of growth factors has been used to promote periodontal regeneration on periodontal ligament (PDL) and cementum defects. A preameloblast-conditioned medium (PA-CM) was prepared from cultured murine apical bud cells, which can differentiate into ameloblasts. We examined the effect of PA-CM on PDL cells and cementoblasts in vitro and evaluated histologically the effects of PA-CM on the regeneration of experimentally induced periodontal defects in vivo. MATERIAL AND METHODS: In vitro, the effects of PA-CM on the migration of human PDL cells were examined using a scratch wound healing assay and a transwell assay. The differentiation and mineralization potential of PA-CM-treated human PDL cells and murine cementoblastic OCCM-30 cells was examined by real-time polymerase chain reaction and Alizarin red-S staining. In vivo, six mongrel dogs (12-16 kg; 6-8 mo old) were used. Twenty-four roots were replanted with either, (i) only periodontal defects (n = 12; control group), or (ii) periodontal defects and PA-CM treatment (n = 12; experimental group). In the experimental group, the PDL and cementum between notches was removed using a Gracey curette and soaked in 0.08 mL water containing 80 µg of a PA-CM for 2 min. The dogs were killed at 4 and 8 wk post-surgery. RESULTS: The in vitro results showed that PA-CM stimulated the migration of PDL cells and promoted the differentiation and mineralization of PDL cells and cementoblasts. Real-time polymerase chain reaction analysis revealed stronger expression of Runx2, Osx, OC, Bsp and Cap mRNAs in the PA-CM-treated PDL cells and cementoblasts than those in the control cells. In vivo, newly formed PDL-like tissue and cementum-like tissue were observed partially between the root surfaces and newly formed bone in the experimental group. The regenerated PDL-like tissue in the experimental group was significantly higher than that in the control group at 8 wk (p < 0.05). The replacement resorption on the experimental group was significantly lower than that in the control group at 8 wk (p < 0.05). In addition, the amount of newly formed cementum-like tissue in the experimental group was significantly higher than that in the control group at 4 and 8 wk (p < 0.05). CONCLUSION: These results suggest that PA-CM has the potential to regenerate periodontal tissues in PDL and cementum defects.
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Cemento Dental/efectos de los fármacos , Ligamento Periodontal/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Adolescente , Animales , Calcificación Fisiológica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ensayos de Migración Celular , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Cementogénesis/efectos de los fármacos , Medios de Cultivo Condicionados , Cemento Dental/lesiones , Perros , Humanos , Ratones Endogámicos C57BL , Tercer Molar , Periodoncio/efectos de los fármacos , Periodoncio/lesiones , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Raíz del Diente/efectos de los fármacos , Raíz del Diente/lesiones , Raíz del Diente/patología , Adulto JovenRESUMEN
Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.
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Neoplasias Esofágicas/cirugía , Estenosis Esofágica/cirugía , Esofagoscopía/instrumentación , Presión , Stents Metálicos Autoexpandibles , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/complicaciones , Estenosis Esofágica/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mast cells release potent mediators that alter enteric nerve and smooth muscle functions and may contribute to the pathogenesis of functional gastrointestinal disorders. The goal of this study was to determine if mucosal mast cell infiltration was associated with smooth muscle segmental changes in esophageal contraction. All patients with noncardiac chest pain (NCCP) were divided into two groups consisting of patients with non-erosive reflux disease or functional chest pain (FCP) according to the results of ambulatory 24 hours esophageal pH monitoring and high-resolution manometry. Pressure-volume (PV) was calculated by multiplying the length of the esophageal segment, duration of the contraction, and mean pressure over the entire space-time box (P mean). Quantification of mast cells was performed in five consecutive nonoverlapping immunostained sections. Spearman correlation analysis showed that the distal segment PV correlated with the mast cell count in all of the patients combined and in patients with FCP with correlation coefficients of 0.509 and 0.436, respectively (P = 0.004 and P = 0.042). Similar findings were observed for the segmental ratio of distal to proximal smooth muscle PV in all patients and in patients with FCP (correlation coefficients 0.566; P = 0.001 and correlation coefficients 0.525; P = 0.012, respectively). Mucosal mast cell infiltration was associated with distal esophageal contraction as a key pathophysiologic factor of NCCP.
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Dolor en el Pecho/fisiopatología , Esófago/fisiopatología , Mastocitos/metabolismo , Contracción Muscular , Músculo Liso/fisiopatología , Adulto , Dolor en el Pecho/etiología , Trastornos de la Motilidad Esofágica/complicaciones , Trastornos de la Motilidad Esofágica/fisiopatología , Monitorización del pH Esofágico , Femenino , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/fisiopatología , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Membrana Mucosa/metabolismo , PresiónRESUMEN
Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47(phox) including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE-/- atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47(phox) promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology.
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Adiponectina/genética , Aterosclerosis/genética , Terapia Genética , Regiones Promotoras Genéticas , Adiponectina/uso terapéutico , Animales , Aterosclerosis/patología , Aterosclerosis/terapia , Células Espumosas/metabolismo , Células Espumosas/patología , Células HeLa , Humanos , Lentivirus/genética , Macrófagos/metabolismo , Ratones , Datos de Secuencia MolecularAsunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Escamosas/prevención & control , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Cutáneas/prevención & control , Xerodermia Pigmentosa/tratamiento farmacológico , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Ipilimumab/uso terapéutico , Masculino , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Resultado del Tratamiento , Xerodermia Pigmentosa/complicaciones , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to identify the socioeconomic factors associated with the prevalence of periodontitis in Koreans. METHODS: Cross-sectional data from 12 763 subjects, 15 years old and above, who underwent periodontal examinations were obtained from the Korean National Health and Nutrition Examination Survey IV (2007-209). Multivariate linear and logistic regression analyses were applied to estimate the association between socioeconomic indicators and prevalence of periodontitis. RESULTS: A significant association was found between increasing age and periodontitis. Participants with higher income were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.78-0.98, and aOR = 0.7 and 95% CI = 0.60-0.80 in the middle and highest quintiles of monthly household income, respectively). In addition, participants living in rural areas were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.81-0.99), and current smokers were more likely to have periodontitis (aOR = 1.7 and 95% CI = 1.49-1.89). The analysis of comorbidities revealed that individuals with diabetes mellitus (DM) were significantly more likely to have periodontitis (aOR = 1.4 and 95% CI = 1.18-1.68). CONCLUSIONS: In a rapidly increasing Korean population, the lower socioeconomic groups as well as individuals with DM were significantly more likely to present with periodontitis.
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Diabetes Mellitus/epidemiología , Disparidades en el Estado de Salud , Renta/estadística & datos numéricos , Periodontitis/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Prevalencia , República de Corea/epidemiología , Población Rural/estadística & datos numéricos , Fumar/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: The purposes of this study were to isolate and characterize stem cells from inflamed pulp tissue of human functional deciduous teeth (iSHFD) and to evaluate the influence of fibroblastic growth factor-2 (FGF-2) on the regenerative potential. MATERIALS AND METHODS: We successfully isolated mesenchymal stem cells (MSCs) from the inflamed dental pulp tissue of human deciduous teeth and demonstrated that their regenerative potential could be enhanced by the application of FGF-2 (20 ng ml(-1)) during ex vivo expansion. Isolated stem cells expanded in FGF-2 were characterized using a colony-forming assay, proliferation, migration, in vitro differentiation, in vivo ectopic transplantation assay, and gene expression profiling. RESULTS: MSCs isolated from the inflamed pulp tissue of functional deciduous teeth potentially possess the qualities of those from human exfoliated deciduous teeth. FGF-2 applied to iSHFD during expansion enhanced the colony-forming efficiency of these cells, increased their proliferation and migration potential, and reduced their differentiation potential in vitro. However, the ectopic transplantation of iSHFD/FGF-2 in vivo increased the formation of dentin-like material. CONCLUSION: FGF-2 expansion of stem cells from inflamed pulp tissues of human deciduous teeth can be a good source of stem cells for future clinical applications and a novel way of using discarded inflamed tissues.
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Pulpa Dental/citología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Pulpitis/patología , Diferenciación Celular , Células Cultivadas , Factor 2 de Crecimiento de Fibroblastos/farmacología , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Diente PrimarioRESUMEN
This study was performed to determine the effect of dietary supplementation of procyanidin on growth performance, blood characteristics, and immune function in growing pigs. In experiment 1 (Exp. 1), thirty-two crossbred pigs with an initial BW of 19.2±0.3 kg were allocated into 4 treatments for an 8-wk experiment: i) CON (basal diet), ii) MOS 0.1 (basal diet+0.1% mannanoligosaccharide), iii) Pro-1 (basal diet+0.01% procyanidin), and iv) Pro-2 (basal diet+0.02% procyanidin). Pigs fed Pro-1 and Pro-2 diets had greater (p<0.05) gain:feed ratio compared with those fed CON or MOS 0.1 diets. Serum creatinine concentration was less (p<0.05) in Pro-2 treatment than those in CON, MOS 0.1 and Pro-1 treatments. In Exp. 2, twelve pigs (BW 13.4±1.3 kg) received basal diet with i) 0 (CON), ii) 0.02% (Pro-0.02%), and iii) 0.04% procyanidin (Pro-0.04%) for 4 wk. Concentration of platelets was lower (p<0.05) in the Pro-0.04% group compared to CON at 24 h after lipopolysaccharide (LPS) challenge. In addition, secretion of cytokines from cultured peripheral blood mononuclear cells (PBMC) in the presence or absence of procyanidin was examined. The levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were lower (p<0.05) in Pro (LPS-stimulated PBMCs+procyanidin) than those in CON (LPS-stimulated PBMCs+PBS) at 4 h after LPS challenge. These data suggest that dietary addition of procyanidin improves feed efficiency and anti-inflammatory cytokines of pigs.
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BACKGROUND AND OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-oxidizing enzyme with immune-inhibitory effects. The aim of this study was to investigate the expression of IDO by lipopolysaccharide (LPS), a component of gram-negative bacteria, in human periodontal ligament (PDL) cells. MATERIAL AND METHODS: Human PDL cells and gingival fibroblasts (GFs) were prepared from explants of human PDLs and from gingival tissues of clinically healthy donors, respectively. Real-time RT-PCR, western blotting and the IDO enzyme assay were performed to determine the expression of IDO following LPS treatment of cells. LPS was injected into mice tail veins to evaluate the effects of LPS in vivo in the maxillary first molar. Immunofluorescence staining and histological analysis were followed to localize IDO in mouse PDL. RESULTS: The level of expression of IDO mRNA in primary human PDL cells after LPS treatment was increased in a dose-dependent manner, reaching a peak 8 h after LPS treatment. The expression and activities of IDO protein were significantly increased in comparison with those of the control. In addition, the increased production of kynurenine in culture medium was observed 72 h after LPS treatment. In the immunofluorescence findings, stronger immunoreactivities were shown in PDL than in gingival tissues in the maxillae. In accordance with the immunofluorescence findings, LPS treatment induced a strong up-regulation of IDO mRNA in human PDL cells, whereas human GFs showed only a weak response to LPS. CONCLUSION: These results clearly show that IDO was induced by LPS in primary human PDL cells, suggesting that PDL might be involved in the regulation of oral inflammatory disease.
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Indolamina-Pirrol 2,3,-Dioxigenasa/efectos de los fármacos , Lipopolisacáridos/farmacología , Ligamento Periodontal/enzimología , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Escherichia coli , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Técnica del Anticuerpo Fluorescente , Encía/citología , Encía/efectos de los fármacos , Encía/enzimología , Humanos , Interleucina-1beta/efectos de los fármacos , Quinurenina/análisis , Quinurenina/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Organismos Libres de Patógenos Específicos , Factores de Tiempo , Regulación hacia ArribaRESUMEN
This study was conducted to evaluate the effects of dietary vitamin levels and stocking densities on growth performance, nutrient digestibility, and blood characteristics in growing pigs. A 2×3 factorial (two vitamin levels, three regimens of stocking densities) arrangement was utilized with 96 pigs (23.10×0.95 kg initial body weight and 63 d of age) for 36 d. The pigs were allocated to pens with different stocking density (0.64, 0.48, and 0.38 m(2)/pig, respectively). The diets used in this study were a normal diet (based on NRC) and a high level of vitamin diet (2-fold higher than normal diet). The ADG and ADFI of pigs were decreased as the stocking density increased (p = 0.03 and p = 0.01, respectively). The G/F of pigs was 5% lower in the high vitamin treatment (p = 0.03) as compared with the control treatment. The apparent total tract digestibility (ATTD) of DM and N digestibility was negatively affected by the high level of vitamin in diets (p = 0.05 and p = 0.04, respectively). Moreover, a significant and negative effect on the ATTD of N was detected in the large groups (linear, p = 0.02). Blood cortisol concentration was increased with increasing stocking density (linear, p = 0.05), and was decreased by high level of vitamin (p = 0.04) at the end of this experiment. Stocking density also caused a linear reduction in WBC concentration (p = 0.05). Our data indicated that the principal effect of stocking density was not reliant on dietary vitamin levels. In conclusion, results indicated that doubling the vitamin supplementation did not improve the growth performance of pigs in high density. However, the blood cortisol concentration was decreased but the ATTD of N digestibility was impaired by high level of vitamin diet.
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BACKGROUND AND OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a well-known growth factor that can induce robust bone formation, and recent studies have shown that rhBMP-2-induced osteogenesis is closely related to adipogenesis. The aim of the present study was to determine the dose- and time-dependent effects of rhBMP-2 on the osteogenic and adipogenic differentiation of human alveolar bone-derived stromal cells (hABCs) in vivo and in vitro. MATERIAL AND METHODS: hABCs were isolated and cultured, and then transplanted using a carrier treated either with or without rhBMP-2 (100 µg/mL) into an ectopic subcutaneous mouse model. Comprehensive histologic and histometric analyses were performed after an 8-wk healing period. To further understand the dose-dependent (0, 10, 50, 200, 500 and 1000 ng/mL) and time-dependent (0, 3, 5, 7 and 14 d) effects of rhBMP-2 on osteogenic and adipogenic differentiation, in vitro osteogenic and adipogenic differentiation of hABCs were evaluated, and the expression of related mRNAs, including those for alkaline phosphatase, osteocalcin, bone sialoprotein, peroxisome-proliferator-activated receptor gamma-2 and lipoprotein lipase, were assessed using quantitative RT-PCR. RESULTS: rhBMP-2 significantly promoted the osteogenic and adipogenic differentiation of hABCs in vivo, and gradually increased both the osteogenic and adipogenic potential in a dose- and time-dependent manner with minimal deviation in vitro. The expression of osteogenesis- and adipogenesis-associated mRNAs were concomitantly up-regulated by rhBMP-2. CONCLUSION: The findings of the present study showed that rhBMP-2 significantly enhanced the adipogenic as well as the osteogenic potential of hABCs in dose- and time-dependent manner. The control of adipogenic differentiation of hABCs should be considered when regenerating the alveolar bone using rhBMP-2.
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Adipogénesis/efectos de los fármacos , Proceso Alveolar/efectos de los fármacos , Proteína Morfogenética Ósea 2/farmacología , Osteogénesis/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Factor de Crecimiento Transformador beta/farmacología , Adulto , Fosfatasa Alcalina/análisis , Proceso Alveolar/citología , Animales , Proteína Morfogenética Ósea 2/administración & dosificación , Regeneración Ósea/fisiología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Hidroxiapatitas/química , Sialoproteína de Unión a Integrina/análisis , Lipoproteína Lipasa/análisis , Ratones , Ratones Endogámicos , Persona de Mediana Edad , Osteocalcina/análisis , PPAR gamma/análisis , ARN Mensajero/análisis , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Células del Estroma/trasplante , Tejido Subcutáneo/cirugía , Factores de Tiempo , Andamios del Tejido/química , Factor de Crecimiento Transformador beta/administración & dosificación , Regulación hacia ArribaRESUMEN
BACKGROUND AND OBJECTIVE: Human periodontal ligament stem cells (hPDLSCs) have been reported to play the pivotal role in periodontal regeneration. However, the dynamic cellular healing process initiated by hPDLSCs still remains to be elucidated. In the present study, the sequence of regeneration by hPDLSCs was assessed using histological and immunohistochemical observation in an ectopic transplantation model, which is a well-standardized assessment tool that excludes the innate healing factors from the animals. MATERIAL AND METHODS: Human periodontal ligament stem cells that were isolated and characterized from teeth (n=12) extracted for the purpose of orthodontic treatment were transplanted with carriers into ectopic subcutaneous pouches in immunocompromised mice (n=20). Animals were killed after several different healing periods: 3 d (n=4), 1 (n=4), 2 (n=4), 4 (n=4) and 8 wk (n=4). Histological analysis for regenerated tissues formed by hPDLSCs was conducted using hematoxylin and eosin, Masson's trichrome and picrosirius red staining. In addition, immunohistochemical staining was performed to observe the sequential expression of osteogenic/cementogenic and periodontal ligament tissue-specific markers associated with periodontal regeneration. RESULTS: The whole healing process by transplanted hPDLSCs could be broadly divided into four distinctive phases. In the first phase, proliferated hPDLSCs migrated evenly all over the carrier, and collagenous tissues appeared in the form of amorphous collagen matrices. In the second phase, collagen fibers were well arranged among the carriers, and cementoid-like tissues were observed. In the third phase, the formation of mature collagen fibers, resembling Sharpey's fibers, was associated with active mineralization of cementum-like tissues, and in the fourth phase, the maturation of cementum-like tissues was observed on carrier surfaces. Various osteogenic/cementogenic markers related to the regeneration processes were expressed in a well-orchestrated time order. Interestingly, well-organized cementum-like and periodontal ligament fiber-like tissues and cells with early and late osteogenic/cementogenic markers were frequently observed in the secluded area of carrier surfaces. We termed this area the cell-rich zone. CONCLUSION: The results from this study clearly demonstrated the sequential histological changes during periodontal tissue regeneration by hPDLSCs. Understanding of this process would potentially enable us to develop better cell-based treatment techniques.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Ligamento Periodontal/citología , Ligamento Periodontal/fisiología , Regeneración/fisiología , Ingeniería de Tejidos/métodos , Fosfatasa Alcalina/biosíntesis , Análisis de Varianza , Animales , Regeneración Ósea/fisiología , Fosfatos de Calcio , Adhesión Celular , Cementogénesis/fisiología , Fenómenos Cronobiológicos , Colágeno Tipo I/biosíntesis , Colágeno Tipo III/biosíntesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Durapatita , Humanos , Técnicas para Inmunoenzimas , Masculino , Ratones , Ratones SCID , Modelos Biológicos , Osteocalcina/biosíntesis , Osteopontina/biosíntesis , Estadísticas no Paramétricas , Tejido Subcutáneo/cirugía , Andamios del TejidoRESUMEN
OBJECTIVE: The human periodontal ligament stem cells (hPDLSCs) and human alveolar bone-derived stromal cells (hABCs) seem to be closely involved in the maintenance of alveolar bone in an anatomically indirect manner; however, there is little study on this matter. Therefore, the effect of hPDLSCs on the osteoclastogenic, osteogenic, and adipogenic differentiation of hABCs was evaluated, focusing on the humoral factors released by hPDLSCs. MATERIALS AND METHODS: Human periodontal ligament stem cells and hABCs were isolated and characterized. hPDLSCs were indirectly cocultured to observe the in vitro effect of humoral factors released from hPDLSCs on the osteoclastogenic, osteogenic, and adipogenic differentiation of hABCs. Human gingival fibroblasts (hGFs) were utilized as positive control. RESULTS: Isolated cells demonstrated the presence of stem cells within. Indirect coculture of hPDLSCs greatly inhibited osteoclastogenesis by hABCs. Osteogenesis/adipogenesis of hABCs was also inhibited by indirect coculture with hPDLSC. The magnitude of regulatory effect from hPDLSCs was significantly greater than that of hGFs. CONCLUSIONS: Humoral factors released from hPDLSCs seemed to modulate the differentiation of hABCs, and the osteoclastogenic, osteogenic, and adipogenic differentiation of hABCs was all inhibited, suggesting the potential role of hPDLSCs in the maintenance of the alveolar bone.
Asunto(s)
Proceso Alveolar/citología , Comunicación Paracrina/fisiología , Ligamento Periodontal/citología , Células Madre/fisiología , Células del Estroma/fisiología , Adipocitos/fisiología , Adipogénesis/fisiología , Adolescente , Adulto , Animales , Recuento de Células , Técnicas de Cultivo de Célula , Diferenciación Celular/fisiología , Separación Celular , Técnicas de Cocultivo , Medios de Cultivo , Fibroblastos/fisiología , Encía/citología , Humanos , Leucocitos Mononucleares/fisiología , Ratones , Ratones SCID , Osteoblastos/fisiología , Osteoclastos/fisiología , Osteogénesis/fisiología , Adulto JovenRESUMEN
While diagnostic overlap exists between gastroesophageal reflux disease and eosinophilic esophagitis especially on histological findings, therapeutic approaches for the two disease entities are very different. Recently, anti-inflammatory treatment, in addition to acid suppressants, has been investigated for gastroesophageal reflux disease. This study investigated whether the incidence of endoscopic erosive esophagitis was lower in recipients of long-term leukotriene receptor antagonist (LTRA) treatment. This retrospective comparative study included 207 recipients of an LTRA and an equal number of controls who underwent screening upper endoscopic examination. Twenty-two (10.6%) and 51 (24.6%) cases of erosive esophagitis were detected in the LTRA and control groups, respectively (P < 0.001). A significantly higher incidence of minimal change esophagitis was also found in the controls compared with the LTRA group (14.5% vs. 2.4%, P < 0.001). On multivariate analysis, LTRA treatment was significantly and inversely associated with erosive esophagitis (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.13 to 0.46). Within the LTRA treatment group, an increased risk of erosive esophagitis was strongly associated with the presence of hiatal hernia (OR, 5.89; 95% CI, 2.20-15.73, P < 0.001) and short duration of LTRA treatment (OR, 0.64; 95% CI, 0.37-0.89, P= 0.022). In conclusion, this preliminary retrospective analysis demonstrated that patients who underwent long-term treatment with a LTRA had low incidence of endoscopic minimal change esophagitis.
Asunto(s)
Acetatos/uso terapéutico , Esofagitis Péptica/tratamiento farmacológico , Reflujo Gastroesofágico/tratamiento farmacológico , Antagonistas de Leucotrieno/uso terapéutico , Quinolinas/uso terapéutico , Adulto , Asma/complicaciones , Asma/tratamiento farmacológico , Índice de Masa Corporal , Estudios de Casos y Controles , Ciclopropanos , Esofagitis Péptica/complicaciones , Esofagoscopía , Femenino , Reflujo Gastroesofágico/complicaciones , Hernia Hiatal/complicaciones , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , SulfurosRESUMEN
A total of 144 pigs ((Landrace×Yorkshire)×Duroc] with an average initial BW of 8.45±0.57 kg were used in a 5-wk growth trial. Pigs were randomly allocated to 4 treatments with 9 replications per pen in a randomized complex block design. Dietary treatments included: i) CON (basal diet), ii) ANT (CON+tylosin 1 g/kg), iii) H1 (CON+H. cordata 1 g/kg) and iv) T1 (CON+T. officinale 1 g/kg). In this study, pigs fed the ANT and T1 treatment had a higher (p<0.05) average daily gain (ADG) and gain:feed (G:F) ratio than those fed CON and H1 treatment. Dietary ANT and T1 treatment led to a higher energy digestibility than the CON group. No difference (p>0.05) was observed on the growth performance and apparent total tract digestibility with H1 supplementation compared with the CON treatment. The inclusion of ANT treatment led to a higher (p<0.05) lymphocyte concentration compared with the CON treatment. Dietary supplementation of herbs did not affect (p>0.05) the blood characteristics (white blood cell (WBC), red blood cell (RBC), IgG, lymphocyte). No difference was observed on (p<0.05) fecal microbial shedding (E. coli and lactobacillus) between ANT and CON groups. Treatments H1 and T1 reduced the fecal E. coli concentration compared with the CON treatment, whereas the fecal lactobacillus concentration was not affected by the herb supplementation (p>0.05). In conclusion, the inclusion of T. officinale (1 g/kg) increased growth performance, feed efficiency, energy digestibility similarly to the antibiotic treatment. Dietary supplementation of T. officinale and H. cordata (1 g/kg) reduced the fecal E. coli concentration in weaning pigs.
RESUMEN
This study was performed to determine the effects of dietary fat sources, i.e., beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the growth performance, meat quality and gene expression in growing-finishing pigs. A total of 72 crossbred pigs (Landrace×Large White×Duroc) were used at 71±1 kg body weight (about 130 d of age) in 24 pens (320×150 cm) in a confined pig house (three pigs per pen) with six replicate pens per treatment. The growing diet was given for periods of 14±3 d and the finishing diet was given for periods of 28±3 d. The fat type had no significant effect either on growth performance or on chemical composition or on meat quality in growing-finishing pigs. Dietary fat type affected fatty acid composition, with higher levels of unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group. Microarray analysis in the Longissimus dorsi identified 6 genes, related to insulin signaling pathway, that were differentially expressed among the different feed groups. Real time-PCR was conducted on the six genes in the longissimus dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level in the olive oil group (respectively, p<0.05, p<0.001). The results of this study indicate that the type of dietary fat affects fatty acid composition and insulin signaling-related gene expression in the LM of pigs.