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1.
J Periodontal Res ; 55(6): 868-876, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32583887

RESUMO

BACKGROUNDS AND OBJECTIVE: Increased neutrophil infiltration and osteoclast formation are key characteristics of periodontitis. The effect of these neutrophils on osteoclast formation in periodontitis remains unclear. Therefore, we investigated the effects of neutrophils on osteoclast formation in a neutrophil-deficient mouse model of periodontitis. METHODS: Anti-Ly6G antibody (Ab) was used for neutrophil depletion in two mouse models: periodontitis and air pouch. In the periodontitis experiments, mice were divided into PBS-administered control (C), control Ab-administered periodontitis (P), and anti-Ly6G Ab-administered periodontitis (P + Ly6G) groups. Periodontitis was induced by ligature of mandibular first molars. In the air pouch experiments, mice were divided into PBS-administered (C), LPS and control Ab-administered (LPS), and LPS and anti-Ly6G Ab-administered (LPS + Ly6G) groups. Neutrophil migration into air pouches was induced by LPS injection. Flow cytometry was used to examine CD11b+ Ly6G+ neutrophils in the blood of periodontitis mice and CD11b+ Ly6G+ RANKL+ neutrophils in exudates of air pouch mice. In periodontal tissue, Ly6G+ neutrophil and RANKL+ cell numbers in periodontal ligament and alveolar bone areas were estimated using immunohistochemistry, osteoclast numbers were measured using TRAP assay, and alveolar bone loss was determined by H&E staining. RESULTS: In blood, CD11b+ Ly6G+ neutrophils were found in greater percentage in the P group than in the C group on days 3 and 7. However, the percentage of neutrophils was lower in the P + Ly6G group than in the C and P groups. In periodontal tissue, the numbers of Ly6G+ neutrophils and RANKL+ cells were lower in the P + Ly6G group than in the P group on day 3. Ly6G+ neutrophil numbers decreased more in the P + Ly6G group than in the P group on day 7, but RANKL+ cell numbers did not decrease in the P + Ly6G group. In exudates, the number of CD11b+ Ly6G+ RANKL+ neutrophils was greater in the LPS group than in the C and LPS + Ly6G groups. On days 3 and 7, the numbers of osteoclasts and alveolar bone loss were greater in periodontal tissue in the P and P + Ly6G groups than in the C group. Interestingly, there were fewer osteoclasts in the P + Ly6G group than in the P group on day 3. CONCLUSION: Neutrophil deficiency caused a reduction in numbers of both RANKL+ cells and osteoclasts in periodontitis-induced tissues only on day 3. Furthermore, in the LPS-injected air pouch model, neutrophil deficiency reduced the influx of RANKL+ neutrophils. These findings suggest that the presence of neutrophils induces RANKL expression and could induce osteoclast formation in the early stages of periodontitis.


Assuntos
Perda do Osso Alveolar , Neutrófilos , Osteoclastos , Periodontite , Ligante RANK/metabolismo , Animais , Camundongos , Neutrófilos/fisiologia , Periodonto
2.
Int J Mol Sci ; 21(12)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575634

RESUMO

Tooth development and regeneration occur through reciprocal interactions between epithelial and ectodermal mesenchymal stem cells. However, the current studies on tooth development are limited, since epithelial stem cells are relatively difficult to obtain and maintain. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be alternative options for epithelial cell sources. To differentiate hESCs/hiPSCs into dental epithelial-like stem cells, this study investigated the hypothesis that direct interactions between pluripotent stem cells, such as hESCs or hiPSCs, and Hertwig's epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cell line may induce epithelial differentiation. Epithelial-like stem cells derived from hES (EPI-ES) and hiPSC (EPI-iPSC) had morphological and immunophenotypic characteristics of HERS/ERM cells, as well as similar gene expression. To overcome a rare population and insufficient expansion of primary cells, EPI-iPSC was immortalized with the SV40 large T antigen. The immortalized EPI-iPSC cell line had a normal karyotype, and a short tandem repeat (STR) analysis verified that it was derived from hiPSCs. The EPI-iPSC cell line co-cultured with dental pulp stem cells displayed increased amelogenic and odontogenic gene expression, exhibited higher dentin sialoprotein (DSPP) protein expression, and promoted mineralized nodule formation. These results indicated that the direct co-culture of hESCs/hiPSCs with HERS/ERM successfully established dental epithelial-like stem cells. Moreover, this differentiation protocol could help with understanding the functional roles of cell-to-cell communication and tissue engineering of teeth.


Assuntos
Polpa Dentária/citologia , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Ligamento Periodontal/citologia , Comunicação Celular , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Células Epiteliais/citologia , Transição Epitelial-Mesenquimal , Humanos , Imunofenotipagem , Engenharia Tecidual
3.
J Transl Med ; 16(1): 306, 2018 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413166

RESUMO

BACKGROUND: Diabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss. Simvastatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone. Therefore, we investigated effect of SIM on tibial and alveolar bone loss in type 1 diabetic rats with periodontitis. METHODS: Rats were divided into control (C), diabetes with periodontitis (DP), and diabetes with periodontitis treated with SIM (DPS) groups. DP and DPS groups were intravenously injected with streptozotocin (50 mg/kg), and C group was injected with citrate buffer. Seven days later (day 0), periodontitis was induced by ligatures of mandibular first molars. DP and DPS groups were orally administered vehicle or SIM (30 mg/kg) from day 0 to days 3, 10, or 20. Alveolar and tibial bone loss was measured using histological and m-CT analysis alone or in combination. Osteoclast number and sclerostin-positive osteocytes in tibiae were evaluated by tartrate-resistant acid phosphatase and immunohistochemical staining, respectively. Glucose, triglyceride (TG), cholesterol (CHO), and low-density lipoprotein (LDL) were evaluated. RESULTS: Consistent with diabetes induction, the DP group showed higher glucose and TG levels at all timepoints and higher CHO levels on day 20 than C group. Compared to the DP group, the DPS group exhibited reduced levels of glucose (day 3), TG (days 10 and 20), CHO, and LDL levels (day 20). Bone loss analysis revealed that the DP group had lower bone volume fraction, bone mineral density, bone surface density, and trabecular number in tibiae than C group at all timepoints. Interestingly, the DPS group exhibited elevation of these indices at early stages compared to the DP group. The DPS group showed reduction of osteoclasts (day 3) and sclerostin-positive osteocytes (days 3 and 20) compared with the DP group. There was no difference in alveolar bone loss between DP and DPS groups. CONCLUSIONS: These results suggest that SIM attenuates tibial, but not alveolar bone loss in type 1 diabetic rats with periodontitis. Moreover, attenuation of tibial bone loss by SIM may be related to inhibition of osteoclast formation and reduction of sclerostin expression.


Assuntos
Reabsorção Óssea/complicações , Reabsorção Óssea/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Periodontite/complicações , Sinvastatina/uso terapêutico , Tíbia/patologia , Perda do Osso Alveolar/sangue , Perda do Osso Alveolar/complicações , Perda do Osso Alveolar/tratamento farmacológico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/metabolismo , Reabsorção Óssea/sangue , Reabsorção Óssea/patologia , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/sangue , Jejum/sangue , Marcadores Genéticos , Lipoproteínas LDL/sangue , Masculino , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Periodontite/sangue , Ratos Endogâmicos F344 , Sinvastatina/farmacologia , Tíbia/efeitos dos fármacos , Triglicerídeos/sangue
4.
J Transl Med ; 16(1): 70, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29544500

RESUMO

BACKGROUND: Periodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth. Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation. Intermittent parathyroid hormone (PTH) administration displays an anabolic effect on bone. In this study, we investigated the effect of intermittent PTH administration on alveolar bone loss in type 1 diabetic rats with periodontitis. METHODS: Rats were divided into control (C), periodontitis (P), periodontitis treated with PTH (P + PTH), diabetes with periodontitis (DP), and diabetes with periodontitis treated with PTH (DP + PTH) groups. To induce type 1 diabetes, rats were injected with streptozotocin and periodontitis was induced bilaterally by applying ligatures to the mandibular first molars for 30 days. During the experimental period, the P + PTH and DP + PTH groups were subcutaneously injected with PTH (40 µg/kg) three times per week, whereas the C, P, and DP groups were injected with citrate buffer. To observe the mineralization of the alveolar bone, the DP and DP + PTH groups were injected with calcein on days 10 and 27, and with alizarin red on day 20. Thirty days after ligation, histological findings and fluorescence labeling were analyzed in the furcations of the mandibular first molars. Sclerostin-positive osteocytes were assessed by immunohistochemical analyses. RESULTS: The DP groups had smaller areas of alveolar bone than the other groups, and the DP + PTH group had a larger alveolar bone area than the DP group. The DP group had less osteoid formation than the C group, whereas the DP + PTH had greater osteoid formation than the DP group. Fluorescence labeling results revealed that the DP + PTH group had more mineral deposition on the alveolar bone than the DP group. The DP + PTH group exhibited lower percentage of sclerostin-positive osteocytes in alveolar bone than the DP group. CONCLUSIONS: Intermittent PTH administration diminishes alveolar bone loss and sclerostin expression in osteocytes, but increases osteoid formation and mineralization, suggesting that intermittent PTH administration attenuates diabetes-aggravated alveolar bone loss by the induction of bone formation. PTH-induced bone formation may be related to the regulation of osteocytic sclerostin expression in type 1 diabetic rats with periodontitis.


Assuntos
Processo Alveolar/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/administração & dosagem , Hormônio Paratireóideo/farmacologia , Periodontite/complicações , Perda do Osso Alveolar/patologia , Processo Alveolar/patologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/patologia , Jejum/sangue , Marcadores Genéticos , Masculino , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Periodontite/sangue , Ratos Endogâmicos F344 , Tíbia/efeitos dos fármacos , Tíbia/patologia
5.
Small ; 13(32)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28692767

RESUMO

Reactive oxygen species (ROS) produced during mitochondrial oxidative phosphorylation play an important role as signal messengers in the immune system and also regulate signal transduction. ROS production, initiated as a consequence of microbial invasion, if generated at high levels, induces activation of the MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway to promote cell survival and proliferation. However, viruses hijack the host cells' pathways, causing biphasic activation of the MEK/ERK cascade. Thus, regulation of ROS leads to concomitant inhibition of virus replication. In the present study, poly(aniline-co-pyrrole) polymerized nanoregulators (PASomes) to regulate intracellular ROS levels are synthesized, exploiting their oxidizing-reducing characteristics. Poly(aniline-co-pyrrole) embedded within an amphiphilic methoxy polyethylene glycol-block-polyphenylalanine copolymer (mPEG-b-pPhe) are used. It is demonstrated that the PASomes are water soluble, biocompatible, and could control ROS levels successfully in vitro, inhibiting viral replication and cell death. Furthermore, the effects of homopolymerized nanoregulators (polypyrrole assembled with mPEG-b-pPhe or polyaniline assembled with mPEG-b-pPhe) are compared with those of the PASomes. Consequently, it is confirmed that the PASomes can regulate intracellular ROS levels successfully and suppress viral infection, thereby increasing the cell survival rate.


Assuntos
Antivirais/farmacologia , Orthomyxoviridae/efeitos dos fármacos , Polímeros/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo
6.
Nat Mater ; 15(6): 669-78, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26950595

RESUMO

We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimetre-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted with direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.


Assuntos
Materiais Biocompatíveis/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Dispositivos Lab-On-A-Chip , Fígado/metabolismo , Monócitos/metabolismo , Miocárdio/citologia , Engenharia Tecidual , Alicerces Teciduais/química , Anastomose Cirúrgica , Animais , Fêmur/irrigação sanguínea , Fêmur/citologia , Fêmur/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Fígado/irrigação sanguínea , Fígado/citologia , Monócitos/citologia , Miocárdio/metabolismo , Porosidade , Ratos , Ratos Endogâmicos Lew , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
7.
J Nanosci Nanotechnol ; 14(11): 8398-404, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25958535

RESUMO

Organically modified xerogels have an advantage over gas sensing applications due to their open, rigid structure and hydrophobicity. Here we evaluated the biocompatibility of xerogel-derived nitric oxide (NO) permeable membranes modified with fluorinated functional groups for application in cellular sensing by growing RAW 264.7 macrophages on them. We examined the cell viability, adhesion and growth of RAW 264.7 macrophages on NO permselective membrane and other cell-adhesive matrices, poly L-lysine and collagen. The surface roughness of each membrane was obtained from topographic atomic force microscopy (AFM) images. In addition, we measured the level of NO release of RAW 264.7 macrophages by lipopolysaccharide (LPS) stimulation using a Griess assay to confirm the function of cells. The fluorinated xerogel-derived membrane had a very smooth surface with rms roughness 2.1 Å and did not show cytotoxic effects in RAW 264.7 macrophages. As a result, the morphology and function of adhering RAW 264.7 macrophage showed no differences from those of other cell-adhesive membranes. Finally, we successfully detected NO release in RAW 264.7 macrophages stimulated by LPS, using a planar-type xerogel-derived NO sensor. Therefore, we suggest that fluorinated xerogel-derived membrane could be used as both a NO permeable and cell-adhesive membrane for cellular sensing applications.


Assuntos
Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flúor/química , Géis/farmacologia , Macrófagos/citologia , Membranas Artificiais , Óxido Nítrico/metabolismo , Animais , Materiais Biocompatíveis/química , Técnicas Biossensoriais , Linhagem Celular , Géis/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Nanotecnologia , Propriedades de Superfície
8.
Acta Odontol Scand ; 72(4): 265-73, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23931568

RESUMO

OBJECTIVE: This study examined the effect of the interaction between periodontitis and type 1 diabetes mellitus on alveolar bone, mandibular condyle and tibia in animal models. MATERIALS AND METHODS: Rats were divided into normal, periodontitis, diabetic and diabetic with periodontitis groups. After injection of streptozotocin to induce diabetes, periodontitis was induced by ligation of both lower-side first molars for 30 days. Alveolar bone loss and trabecular bone volume fraction (BVF) of the mandibular condyle and tibia were estimated via hematoxylin and eosin staining and micro-computed tomography, respectively. Osteoclastogenesis of bone marrow cells isolated from tibia and femur was assayed using tartrate-resistant acid phosphatase staining. RESULTS: The cemento-enamel junction to the alveolar bone crest distance and ratio of periodontal ligament area in the diabetic with periodontitis group were significantly increased compared to those of the periodontitis group. Mandibular condyle BVF did not differ among groups. The BVF of tibia in the diabetic and diabetic with periodontitis groups was lower than that of the normal and periodontitis groups. Osteoclastogenesis of bone marrow cells in the diabetic groups was higher than that in the non-diabetic groups. However, the BVF of tibia and osteoclastogenesis in the diabetic with periodontitis group were not significantly different than those in the diabetic group. CONCLUSIONS: Type 1 diabetes mellitus aggravates alveolar bone loss induced by periodontitis, but periodontitis does not alter the mandibular condyle and tibia bone loss induced by diabetes. Alveolar bone, mandibular condyle and tibia may have different responses to bone loss stimuli in the diabetic environment.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Côndilo Mandibular/patologia , Periodontite/complicações , Tíbia/patologia , Sequência de Bases , Primers do DNA , Diabetes Mellitus Tipo 1/patologia , Humanos , Periodontite/patologia , Reação em Cadeia da Polimerase em Tempo Real , Microtomografia por Raio-X
9.
BMC Oral Health ; 14: 84, 2014 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-25008200

RESUMO

BACKGROUND: There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99). METHODS: Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed. RESULTS: The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis. CONCLUSIONS: Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis.


Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 16/genética , Periodontite Crônica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Cromossomos Humanos Par 21/genética , Periodontite Crônica/etnologia , Complicações do Diabetes , Etnicidade/genética , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fumar , População Branca/genética
10.
Transl Stroke Res ; 15(2): 388-398, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-36639607

RESUMO

There is insufficient evidence on the effect of nanoparticles, particularly liposomes loaded with a statin, on acute ischemic stroke. We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on the outcomes in rats with cerebral ischemia-reperfusion. PEGylated liposome loaded with atorvastatin was developed as a nanoparticle to specifically accumulate in an ischemic region and release the drug to ameliorate the harmful effects of the stroke. LipoStatin was administered to rats with transient middle cerebral artery occlusion through the tail vein immediately after reperfusion (LipoStatin group). LipoStatin efficiently accumulated at the cerebral ischemic injury site of the rat. The LipoStatin group showed a significantly reduced infarct volume (p < 0.01) in brain micro-MR imaging and improved neurological function recovery compared to the control group (p < 0.05). In addition, markedly improved brain metabolism using fluorine-18 fluorodeoxyglucose micro-PET/CT imaging was demonstrated in the LipoStatin group compared with the control group (p < 0.01). Mechanistically, as a result of evaluation through IL-1 beta, TNF-alpha, ICAM-1, and Iba-1 mRNA expression levels at 5 days after cerebral ischemia, LipoStatin showed significant anti-inflammatory effects. Protein expression of occludin, JAM-A, Caveolin-1, and eNOS by western blot at 3 days and fluorescent images at 7 days showed considerable recovery of blood-brain barrier breakdown and endothelial dysfunction. PEGylated LipoStatin can be more effectively delivered to the ischemic brain and may have significant neuroprotective effects. Thus, PEGylated LipoStatin can be further developed as a promising targeted therapy for ischemic stroke and other major vascular diseases.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Ratos , Animais , Atorvastatina/uso terapêutico , Lipossomos/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Polietilenoglicóis/uso terapêutico
11.
Stem Cells Dev ; 33(7-8): 189-199, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38366745

RESUMO

Research on tooth regeneration using human-induced pluripotent stem cells (hiPSCs) is valuable for autologous dental regeneration. Acquiring mesenchymal and epithelial cells as a resource for dental regeneration is necessary because mesenchymal-epithelial interactions play an essential role in dental development. We reported the establishment of hiPSCs-derived dental epithelial-like cell (EPI-iPSCs), but hiPSCs-derived dental mesenchymal stem cells (MSCs) have not yet been reported. This study was conducted to establish hiPSCs-derived MSCs and to differentiate them into dental cells with EPI-iPSCs. Considering that dental MSCs are derived from the neural crest, hiPSCs were induced to differentiate into MSCs through neural crest formation to acquire the properties of dental MSCs. To differentiate hiPSCs into MSCs through neural crest formation, established hiPSCs were cultured and differentiated with PA6 stromal cells and differentiated hiPSCs formed neurospheres on ultralow-attachment plates. Neurospheres were differentiated into MSCs in serum-supplemented medium. Neural crest-mediated MSCs (NC-MSCs) continuously showed typical MSC morphology and expressed MSC markers. After 8 days of odontogenic induction, the expression levels of odontogenic/mineralization-related genes and dentin sialophosphoprotein (DSPP) proteins were increased in the NC-MSCs alone group in the absence of coculturing with dental epithelial cells. The NC-MSCs and EPI-iPSCs coculture groups showed high expression levels of amelogenesis/odontogenic/mineralization-related genes and DSPP proteins. Furthermore, the NC-MSCs and EPI-iPSCs coculture group yielded calcium deposits earlier than the NC-MSCs alone group. These results indicated that established NC-MSCs from hiPSCs have dental differentiation capacity with dental epithelial cells. In addition, it was confirmed that hiPSCs-derived dental stem cells could be a novel cell source for autologous dental regeneration.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Mesenquimais , Humanos , Diferenciação Celular , Transição Epitelial-Mesenquimal , Técnicas de Cocultura , Células Cultivadas
12.
Biomacromolecules ; 14(5): 1618-26, 2013 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-23590189

RESUMO

Oxidative stress is induced by accumulation of hydrogen peroxide (H2O2), and therefore, H2O2 could serve as a potential biomarker of various oxidative stress-associated inflammatory diseases. Vanillin is one of the major components of natural vanilla and has potent antioxidant and anti-inflammatory activities. In this work, we developed a novel inflammation-responsive antioxidant polymeric prodrug of vanillin, termed poly(vanillin oxalate) (PVO). In design, PVO incorporates H2O2-reacting peroxalate ester bonds and bioactive vanillin via acid-responsive acetal linkages in its backbone. Therefore, in cells undergoing damages by oxidative stress, PVO readily degrades into three nontoxic components, one of which is antioxidant and anti-inflammatory vanillin. PVO nanoparticles exhibit potent antioxidant activities by scavenging H2O2 and inhibiting the generation of ROS (reactive oxygen species) and also reduce the expression of pro-inflammatory cytokines in activated macrophages in vitro and in vivo. We, therefore, anticipate that PVO nanoparticles have great potential as novel antioxidant therapeutics and drug delivery systems for ROS-associated inflammatory diseases.


Assuntos
Anti-Inflamatórios/síntese química , Antioxidantes/síntese química , Benzaldeídos/química , Dioxanos/síntese química , Peróxido de Hidrogênio/química , Nanopartículas/química , Poliésteres/síntese química , Pró-Fármacos/síntese química , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Biomarcadores/química , Dioxanos/farmacocinética , Dioxanos/farmacologia , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Nanopartículas/uso terapêutico , Estresse Oxidativo , Poliésteres/farmacocinética , Poliésteres/farmacologia , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese
13.
Artigo em Inglês | MEDLINE | ID: mdl-36767897

RESUMO

This study explored the epidemiological role of central adiposity and body mass index (BMI) in terms of clinical attachment loss (CAL)/pocket depth (PD) and metabolic syndrome components. This study included data from the National Health and Nutrition Examination Survey III of America on 12,254 adults aged 20 years of age or older with a blood sample, anthropometric measurements, and a periodontal examination. Clinical periodontitis measurements, including CAL and PD, were classified into quintiles or quartiles and compared. CAL was positively associated with central adiposity, hypertension, and hyperglycemia; the relationship between CAL and diabetes was stronger when central adiposity was absent (odds ratio [OR] and 95% confidence interval: 6.33, 2.14-18.72 vs. 3.14, 1.78-5.56). The relationship between CAL and impaired fasting glucose (IFG) differed slightly with BMI. The IFG ORs for normal, overweight, and obese patients were 1.63 (1.08-2.45), 1.76 (1.05-2.97), and 1.43 (0.88-2.30), respectively. CAL was positively correlated with all metabolic syndrome components except hypertriglyceridemia. Associations between CAL, diabetes, and IFG significantly varied with BMI. Periodontitis in individuals without central obesity or with normal bodyweight may independently indicate diabetes and IFG. Therefore, preventive measures against periodontitis without obesity are necessary to improve general and oral health.


Assuntos
Síndrome Metabólica , Periodontite , Estado Pré-Diabético , Adulto , Humanos , Estados Unidos/epidemiologia , Adulto Jovem , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Adiposidade , Inquéritos Nutricionais , Glicemia , Periodontite/epidemiologia , Periodontite/complicações , Obesidade/complicações , Obesidade Abdominal/complicações
14.
Adv Sci (Weinh) ; 10(27): e2303429, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37518771

RESUMO

Myocardial infarction (MI) is one of the leading causes of death and disability. Recently developed cardiac patches provide mechanical support and additional conductive paths to promote electrical signal propagation in the MI area to synchronize cardiac excitation and contraction. Cardiac patches based on conductive polymers offer attractive features; however, the modest levels of elasticity and high impedance interfaces limit their mechanical and electrical performance. These structures also operate as permanent implants, even in cases where their utility is limited to the healing period of tissue damaged by the MI. The work presented here introduces a highly conductive cardiac patch that combines bioresorbable metals and polymers together in a hybrid material structure configured in a thin serpentine geometry that yields elastic mechanical properties. Finite element analysis guides optimized choices of layouts in these systems. Regular and synchronous contraction of human induced pluripotent stem cell-derived cardiomyocytes on the cardiac patch and ex vivo studies offer insights into the essential properties and the bio-interface. These results provide additional options in the design of cardiac patches to treat MI and other cardiac disorders.


Assuntos
Células-Tronco Pluripotentes Induzidas , Infarto do Miocárdio , Humanos , Implantes Absorvíveis , Miócitos Cardíacos , Polímeros/química , Tecnologia
15.
Biotechnol Bioeng ; 109(12): 2987-96, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22711504

RESUMO

We investigated growth kinetics of microalgae, Chlorella vulgaris, in immobilized arrays of nanoliter-scale microfluidic drops. These static drop arrays enabled simultaneous monitoring of growth of single as well as multiple cells encapsulated in individual droplets. To monitor the growth, individual drop volumes were kept nearly intact for more than a month by controlling the permeation of water in and out of the microfluidic device. The kinetic growth parameters were quantified by counting the increase in the number of cells in each drop over time. In addition to determining the kinetic parameters, the cell-size distribution of the microalgae was correlated with different stages of the growth. The single-cell growth kinetics of C. vulgaris showed significant heterogeneity. The specific growth rate ranged from 0.55 to 1.52 day(-1) for different single cells grown in the same microfluidic device. In comparison, the specific growth rate in bulk-scale experiment was 1.12 day(-1). It was found that the average cell size changes significantly at different stages of the cell growth. The mean cell-size increased from 5.99 ± 1.08 to 7.33 ± 1.3 µm from exponential to stationary growth phase. In particular, when multiple cells are grown in individual drops, we find that in the stationary growth phase, the cell size increases with the age of cell suggesting enhanced accumulation of fatty acids in older cells.


Assuntos
Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Chlorella vulgaris/crescimento & desenvolvimento , Microalgas/crescimento & desenvolvimento , Técnicas Analíticas Microfluídicas/instrumentação , Análise Serial de Tecidos/instrumentação , Tamanho Celular , Dimetilpolisiloxanos/química , Desenho de Equipamento , Óleo Mineral/química , Distribuição de Poisson
16.
J Prosthet Dent ; 105(3): 164-70, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21356408

RESUMO

STATEMENT OF PROBLEM: It is difficult to achieve a reliable bond between the titanium copings and veneering porcelain of restorations. PURPOSE: The purpose of this study was to investigate the effect of various treatments on the fracture load of bonded titanium and porcelain components of crown restorations. MATERIAL AND METHODS: In this study, the surfaces of titanium copings (n=6) were either airborne-particle abraded with Al(2)O(3) particles, sputter coated with gold, or coated with TiN. Gold ceramic crowns served as the control group (n=6). The effects of these treatments on the fracture load of bonded titanium and low-fusing porcelain were investigated. A universal testing machine was used to determine the fracture load (N) of the crowns. All data were compared using 1-way ANOVA and the post hoc multiple range Tukey test (α=.05). In addition, the metal ceramic interfaces were examined by scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS). RESULTS: The gold-coated titanium (1035 +/-41 N) and TiN-coated titanium (969 +/-93 N) had significantly higher fracture loads (P<.001) than the airborne-particle-abraded titanium ceramic crowns (865+/-44 N). The gold-coated and TiN-coated titanium specimens demonstrated fracture loads similar to that of gold ceramic crowns (1026 +/-50 N) [corrected]. SEM/EDS showed that after the crowns fractured, the gold control group and gold- and TiN-coated titanium specimens had more adherent porcelain on their surfaces than the uncoated titanium that was airborne-particle abraded with Al(2)O(3) particles. CONCLUSIONS: The in vitro fracture load of titanium crowns coated with gold or titanium nitride and bonded to low-fusing porcelain is comparable to that of gold ceramic crowns, and higher than loads observed with uncoated titanium airborne-particle abraded with Al(2)O(3) particles.


Assuntos
Materiais Revestidos Biocompatíveis/química , Ligas Dentárias/química , Colagem Dentária , Materiais Dentários/química , Porcelana Dentária/química , Ligas de Ouro/química , Titânio/química , Adesividade , Óxido de Alumínio/química , Ligas de Cromo/química , Coroas , Corrosão Dentária/métodos , Análise do Estresse Dentário/instrumentação , Humanos , Teste de Materiais , Ligas Metalo-Cerâmicas/química , Microscopia Eletrônica de Varredura , Espectrometria por Raios X , Estresse Mecânico , Propriedades de Superfície
17.
J Gynecol Oncol ; 31(2): e15, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31912673

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea. METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013-2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR). RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923-1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group. CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533.


Assuntos
Carboplatina/uso terapêutico , Doxorrubicina/análogos & derivados , Neoplasias das Tubas Uterinas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Estudos de Coortes , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Intervalo Livre de Progressão , República da Coreia , Estudos Retrospectivos
18.
Nutrients ; 11(5)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075833

RESUMO

Dairy food consumption is known to be inversely associated with periodontal disease. However, there are conflicting results depending on the type of dairy foods. The aim of this study was to determine the relationship between individual dairy food consumption and periodontal disease. A total of 9798 Korean adults, aged ≥30 years, who participated in the fifth and sixth Korea National Health and Nutrition Examination Survey were included in this study's analysis. Dairy food consumption was measured by the semi-quantitative food frequency questionnaire. Periodontal disease was defined as Community Periodontal Index score ≥3 in more than one of six sextants. Frequent intake of dairy foods (≥7 servings/week) was associated with a 24% lower prevalence of periodontal disease compared with never consumers after adjustment for age, gender, income, education, smoking, alcohol consumption, body mass index, diabetes mellitus status, calcium intake, tooth brushing frequency, and use of dental floss (Odds ratio (OR)= 0.76, 95% CI = 0.63-0.91, p for trend = 0.052). Also, frequent intake of milk (≥7 servings/week) was associated with a 26% lower prevalence of periodontal disease after adjustment for potential confounders (OR = 0.74, 95% CI = 0.61-0.89, p for trend = 0.022). Frequent consumption of dairy food including milk may have a beneficial effect on periodontal disease in the Korean adult population.


Assuntos
Dieta , Comportamento Alimentar , Leite/química , Nutrientes/uso terapêutico , Doenças Periodontais/prevenção & controle , Iogurte , Adulto , Animais , Cálcio/uso terapêutico , Caseínas , Laticínios , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Probióticos/uso terapêutico , República da Coreia , Soro do Leite
19.
J Occup Health ; 61(4): 297-304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30839156

RESUMO

OBJECTIVES: In dental clinics, dental hygienists are exposed to aerosolized pathologic bacteria, which can be transmitted to the oral cavity via lip cosmetics. Accordingly, such contamination poses a consistent health risk among staffs. Our study examined the bacterial contamination of lip cosmetics used by dental hygienists while in a clinic setting. METHODS: Sixteen dental hygienists were surveyed regarding their job assignments and habits associated with lip cosmetic. Subsequently, microorganisms were analyzed in collected samples of the hygienists' lip cosmetics using colony-forming unit (CFU) assays, 16s-rDNA polymerase chain reaction, and DNA sequencing. RESULTS: Notably, 81.3% of the submitted lip cosmetic samples were contaminated, with bacterial CFUs ranging from undetectable to innumerable. Many samples (43.8%) exceeded the microbial limits of cosmetic contamination. Of the lip cosmetic used for more than 6 months, 60% exceeded the microbial limit. When wearing a mask every time, only one of the six samples exceeded the microbial limit. More frequent dental mask changing was associated with a lower likelihood that the cosmetic sample would exceed the microbial limit. No samples from hygienists who changed their masks four times a day exceeded the microbial limit, compared to 33.3% from hygienists who only changed the mask when it became wet. Most isolated bacteria were gram-positive, facultative anaerobic, asporogenic, and opportunistically pathogenic, and the most prevalent species were Staphylococcus aureus, Streptococcus salivarius, and Staphylococcus epidermidis. CONCLUSION: Our findings indicate that dental staff, including dental hygienists, should exercise more careful workplace habits, particularly with regard to infection control and cosmetic use.


Assuntos
Bactérias/isolamento & purificação , Cosméticos , Higienistas Dentários , Lábio/microbiologia , Exposição Ocupacional , Adulto , Microbiologia do Ar , Estudos Transversais , Feminino , Humanos , Projetos Piloto , Dispositivos de Proteção Respiratória , Inquéritos e Questionários , Adulto Jovem
20.
J Dent Sci ; 13(1): 13-19, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30895089

RESUMO

BACKGROUND/PURPOSE: To evaluate the degree of wear on human teeth and the cleaning effect of abrasive-free dentifrice. A sodium pyrophosphate and cellulose-containing abrasive-free dentifrice and calcium carbonate-containing control dentifrice were evaluated. MATERIALS AND METHODS: Dentin and enamel specimens were subjected to 109,500 successive double strokes and 5480 double strokes in pH-cycling condition. A profilometer measured abrasion depth. The cleaning effect of dentifrices on artificial stain was evaluated by cleaning power (modified Stookey method) and by removal of colored stain on artificial tooth. RESULTS: The experimental results were evaluated using Mann-Whitney U test. The abrasion depth in dentin specimens was 13.97-26.73 times smaller with abrasive-free dentifrice than with control dentifrice. The abrasion depth of enamel specimen was 2.17 ± 0.66 µm with control dentifrice. The values for abrasive-free dentifrice were too small to measure. In pH-cycling conditions using dentin specimens, abrasion depth was 14.28-19.00 times smaller with abrasive-free dentifrice than with control dentifrice. The cleaning power and removing effect of colored stain were statistically insignificant between abrasive-free dentifrice and control dentifrice (P > 0.05). CONCLUSION: The abrasive-free dentifrice was as effective as control dentifrice in its cleaning effect on artificial stain and can significantly reduce tooth wear more than control dentifrice.

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