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1.
J Periodontal Res ; 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33533512

RESUMEN

BACKGROUND/OBJECTIVES: Iron homeostasis plays a crucial role in the combat against pathogen invasion. Ferrous iron can trigger generous production of reactive oxygen species (ROS) by Fenton reaction. Nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor to deliver ferritin to lysosome, may trigger release of ferritin-bound iron into the cytosol. The aim of the present study was to explore whether NCOA4-mediated ferritinophagy participated in the pathogenesis of periodontitis, and its role in promoting the periodontal inflammation. METHODS: Inflamed and healthy periodontal tissues were harvested for immunobiological staining of ferritinophagy-related genes in the periodontal tissues, while real-time quantitative PCR (qPCR) was utilized to detect mRNA transcription. Periodontal ligament fibroblasts (PDLFs) were isolated and infected with Porphyromonas gingivalis. The mRNA transcription and protein expression of genes involved in the iron metabolism, including NCOA4, transferrin receptor 1 (TFR1), and ferroportin (SLC40A1) were detected by qPCR and western blot. Levels of labile iron pool and ROS production were detected by flow cytometry and confocal endoscopy. Small interference RNA was utilized to knock down NCOA4. RESULTS: Elevated expression of NCOA4, ferritin heavy chain, and light chain were observed in the diseased periodontal tissues. P. gingivalis infection promoted expression of TFR1, NCOA4, and microtubule-associated protein 1-light chain 3 B (LC3B), enhanced levels of intracellular labile iron pool and ROS production. NCOA4 knockdown reduced ROS generation in PDLFs in response to P. gingivalis and mitigated production of pro-inflammatory monocyte chemoattractant protein-1 and interleukin 6. P. gingivalis triggered activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling pathway. In addition, inhibitors of JNK, SP600125, and inhibitors of p38, SB203580 blocked NCOA4 transcription. CONCLUSION: NCOA4-ferritinophagy participated in the progress of periodontitis progression. P. gingvalis-triggered ferritinophagy aggravated production of ROS and inflammatory responses in PDLFS. These findings suggest iron homeostasis plays an important role in the pathogenesis of periodontitis.

2.
Cell Death Discov ; 6(1): 119, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33298848

RESUMEN

Loss of periodontal ligament fibroblasts (PDLFs) is one critical issue for regenerating lost periodontal tissues. A wide variety of regulated cell death pathways, such as apoptosis, pyroptosis, and necroptosis have been proposed in the periodontitis development. The aim of the present study was to explore whether long-term periodontitis-level butyrate may trigger ferroptosis, a newly characterized iron-dependent regulated cell death in PDLFs. Here, we showed that long-term treatment of butyrate, an important short-chain fatty acid in the periodontal pocket, induces the cargo receptor nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and ferroptosis in PDLFs. Butyrate-induced iron accumulation, reactive oxygen species (ROS) generation, glutathione depletion and lipid peroxidation in PDLFs, and the butyrate-induced ferroptosis can be blocked by the lipid peroxide scavenger ferrostatin-1. The NCOA4-mediated ferritinophagy is dependent on p38/hypoxia inducible factor-1α (HIF-1α) pathway activation as well as Bromodomain-containing protein (BRD) 4 and cyclin-dependent kinase 9 (CDK9) coordination. These lines of evidence provide a new mechanistic insight into the mechanism of loss of PDLFs during periodontitis development, showing that periodontitis-level butyrate disrupted iron homeostasis by activation of NCOA4-mediated ferritinophagy, leading to ferroptosis in PDLFs.

3.
Arch Oral Biol ; 121: 104963, 2020 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-33157496

RESUMEN

OBJECTIVE: The purpose of the present study was to explore the sequential changes in the cellular metabolism in gingival fibroblasts (GFs) in response toPorphyromonas gingvalis (P. gingivalis) ATCC33277 infection. DESIGN: GFs were treated withP. gingivalis at the MOI of 50 for 4, 24 and 48 h to mimic the early, medium, and late phase in the bacterial infection. LDH assay and cell counting kit-8 were utilized to explore cell death and proliferation. Real-time PCR was utilized to explore the gene transcription of pro-inflammatory genes. The relative levels of biomolecules in GFs were measured by gas chromatography-mass spectrometry. Principal component analysis and orthogonal partial least-squares-discriminant analysis were performed to visualize the metabolic difference among experimental groups. In addition, pathway analysis was conducted regarding differential metabolites in GFs. RESULTS: P. gingivalis infection triggered significant gene transcription of IL-1ß, IL 6, MCP 1, and MMP 1 in GFs. In addition, P. gingivalis stimulated cell proliferation of GFs at MOI of 10, 50 and 250. Moreover, P. gingivalis triggered significant cell death at higher MOI. 69, 173 and 148 metabolites were qualitatively detected at 4, 24 and 48 h after P. gingivalis infection respectively in GFs, showing a sequential change of different phase. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that ATP-binding cassette transporters, glutathione, purine and pyrimidine metabolism was significantly altered in different phase. CONCLUSIONS: Human GFs may sequentially rewire metabolomics to shape the inflammatory responses and support the proliferation of host cells during P. gingivalis infection.

4.
Head Face Med ; 16(1): 29, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33213460

RESUMEN

BACKGROUND: Periodontal health is of great concern for periodontists and orthodontists in the inter-disciplinary management of patients with bimaxillary protrusion. The aim of present study is to investigate changes in the alveolar bone in the maxillary incisor region and to explore its relationship with displacement of root apex as well as changes in the inclination of maxillary incisors during incisor retraction. METHODS: Samples in this retrospective study consisted of 38 patients with bimaxillary protrusion. Cone-beam computed tomography (CBCT) images was taken before(T0) and after (T1) treatment. Alveolar bone thickness (ABT), height (ABH) and area (ABA) were utilized to evaluate changes in the alveolar bone, while incisor inclination and apex displacement were used to assess changes in the position of maxillary central and lateral incisors. Correlations between alveolar bone remodeling and apex displacement as well as changes in the inclination were investigated. RESULTS: The labial ABT of central and lateral incisors at the mid-root third was increased. In contrast, the palatal ABT at crestal, mid-root and apical third level were consistently decreased. ABH was not altered on the labial side, while significantly decreased on the palatal side. ABA was not significantly increased on the labial side, but significantly decreased on the palatal side, leading to a significantly reduced total ABA. Orthodontic treatment significantly reduced inclination of upper incisors. Changes in the amount (T1-T0) of ABA was remarkably correlated with apex displacement and changes of inclination (T1-T0); in addition, using the multivariate linear regression analysis, changes of ABA on the palatal side (T1-T0) can be described by following equation: Changes of palatal ABA (T1-T0) = - 3.258- 0.139× changes of inclination (T1-T0) + 2.533 × apex displacement (T1-T0). CONCLUSIONS: Retraction of incisors in bimaxillary protrusion patients may compromise periodontal bone support on the palatal side. An equation that incorporated the displacement of root apex and change in the incisor inclination may enable periodontist-orthodontist interdisciplinary coordination in assessing treatment risks and developing an individualized treatment plan for adult patients with bimaxillary protrusion. Moreover, the equation in predicating area of alveolar bone may reduce the risks of placing the teeth out of the bone boundary during 3D digital setups.


Asunto(s)
Incisivo , Técnicas de Movimiento Dental , Adulto , Remodelación Ósea , Cefalometría , Tomografía Computarizada de Haz Cónico , Humanos , Incisivo/diagnóstico por imagen , Maxilar/diagnóstico por imagen , Estudios Retrospectivos
5.
Am J Orthod Dentofacial Orthop ; 158(6): 868-877, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33008709

RESUMEN

This case report describes the treatment of a patient with congenital loss of both mandibular lateral incisors and severely retroclined maxillary incisors. The treatment included bilateral extraction of the maxillary first premolars, accurate 3-digital setup, a 2-stage torque control strategy, and intricate mechanic management. The dilemma of tooth-size discrepancy was solved by ideal torque control to avoid interproximal enamel reduction. An ideal Class I molar and canine relation, as well as canine guidance in the lateral excursion movement, was achieved with good stability.


Asunto(s)
Incisivo , Diente Molar , Diente Premolar , Oclusión Dental , Humanos , Maxilar/diagnóstico por imagen
6.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(4): 393-397, 2020 Aug 01.
Artículo en Chino | MEDLINE | ID: mdl-32865357

RESUMEN

OBJECTIVE: To evaluate the effectiveness of periodontal endoscope as an adjuvant therapy for the non-surgical periodontal treatment of patients with severe and generalized periodontitis. METHODS: Patients (n=13) were divided into three groups: patients treated with conventional subgingival scaling and root planing (SRP) (n=7, 408 sites) (group A), SRP using periodontal endoscope (n=4, 188 sites) (group B) or SRP with periodontal endoscope 3 months after initial SRP (n=2, 142 sites) (group C). Two subgroups were divided into 2 subgroups according to PD at the baseline: 46 mm as subgroup 2. Probing depth (PD), attachment loss (AL), gingival recession (GR) and bleeding on probing (BOP) were recorded. RESULTS: The results of 3 months after treatment showed all PD, AL, and GR values in group A1 were less than those in group B1 (P<0.05), but no significant difference in BOP was found between the two groups. The decrease in PD, BOP in group B2 was more obvious than those in group A2 (P<0.000 1), and the GR values in group B2 were more than those in group A2 (P<0.000 1). But the improvement of AL showed no statistical difference between the two groups (P=0.296 8). In group C1, no significant difference in PD, AL, and GR was observed after endoscopy-assisted therapy, but it was more effective for BOP (P<0.000 1). In group C2, the improvement in PD and AL was significantly different from the improvement in SRP alone (P=0.000 5, P=0.000 2) and was accompanied by more GR (P=0.000 5). CONCLUSIONS: In non-surgical treatment of severe and generalized periodontitis, SRP can achieve good therapeutic effect on sites with 46 mm, the application of periodontal endoscopy can increase the effect, reducing PD and GR, which may be an effective supplement to the current non-surgical periodontal treatment.


Asunto(s)
Raspado Dental , Periodontitis , Endoscopios , Estudios de Seguimiento , Hemorragia Gingival , Humanos , Pérdida de la Inserción Periodontal , Índice Periodontal , Bolsa Periodontal , Aplanamiento de la Raíz , Resultado del Tratamiento
7.
Aging Cell ; 19(10): e13241, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32935456

RESUMEN

Currently, the world's aging population is expanding rapidly, leading to a rise in aged hematopoietic cell transplantation (HCT) recipients and aged donors. However, the age of donors is negatively related to the prognosis after transplantation due to functional decline in hematopoietic stem cells (HSCs) during aging. Previously, we showed that an early-onset dietary restriction (DR) significantly retards early aging of HSCs. However, the effects of a mid-onset DR on HSCs remain unknown. In the current study, we performed 30% DR in 15- to 18-month-old mice (equivalent to 50-60 human years) for short-term (4 months) and long-term (9 months). We show that DR reduces and rectifies the imbalance of the HSC pool in aged mice. Short-term DR improves hematopoietic reconstitution in purified HSC transplantations, but not in bone marrow transplantations. Intriguingly, long-term mid-onset DR improves the hematopoietic regeneration of aging HSCs with a particular enhancement of lymphoid outputs even in total bone marrow transplantation settings. Mechanistically, long-term DR rejuvenates the aberrantly regulated mitochondrial pathways in aging HSCs and is accompanied by increased quiescence and reduced DNA damage signaling in HSCs. Short-term DR showed a similar trend of rescuing these aging hallmarks but to a much lesser extent. Together, the current study suggests that mid-onset DR ameliorates the function of aging HSCs and long-term DR even improved hematopoietic reconstitution in bone marrow transplantation, which could potentially have considerable implications in HCT of humans when only old donors are available.

8.
Orthod Craniofac Res ; 23(4): 509-516, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32583548

RESUMEN

OBJECTIVE: Appropriate torque expression contributes to ideal treatment outcomes both clinically and aesthetically. Whether active and passive self-ligating brackets (SLBs) have different torque-control capability in vivo has never been reported. The purpose of present study was to explore whether there was difference in torque expression in active and passive SLBs. SETTING AND SAMPLE POPULATION: In this retrospective study, 225 patients with four first premolar extractions were enrolled. For each patient, the digital lateral cephalometric radiographs were taken before and after treatment. MATERIALS AND METHODS: The study consisted of 2 groups: 111 subjects were treated with passive SLBs (Damon Q, Ormco) and 114 subjects with active SLBs (Empower 2, American Orthodontics). Measurements to determine skeletal changes and incisor inclination were obtained from cephalometric tracings using Dolphin software (version 11.8, USA). Comparisons in both groups and intergroups were compared using t tests and chi-square test. RESULTS: Significant differences in the variation of U1-SN(°), U1-NA(°), L1-NB(°) and L1-FH(°) were found between two groups. More labially inclined maxillary incisors were found in active SLB group, while more labially inclined mandibular incisors were observed in passive SLB group. CONCLUSIONS: With the present prescription set in the two brackets, active SLBs achieved more proclined maxillary incisors and retroclined mandibular incisors. Clinicians should take torque expression of brackets into consideration during orthodontic treatment.


Asunto(s)
Diseño de Aparato Ortodóncico , Soportes Ortodóncicos , Diente Premolar , Humanos , Alambres para Ortodoncia , Estudios Retrospectivos , Torque
9.
Inflammation ; 43(6): 2061-2074, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32556803

RESUMEN

The host innate immune response stands at the first line of defense against the outburst of pathogen invasion and their byproduct release. The balanced and coordinated expression of genes in normal immune responses is compromised in the progress of endotoxemia with exacerbated inflammation and massive cell death. In the present study, we identified cyclin-dependent kinase 9 (CDK9), the functional subunit of the positive transcription elongation factor b, as a master regulator of inflammatory gene transcription in the process of promoter-proximal pausing to productive elongation. Therapeutic pharmacological inhibition of CDK9 by flavopiridol (FVD) rescued mice from death in experimental models of fatal endotoxemia. In addition to alleviation of the cytokine storm in the circulation system following lethal endotoxin injection, FVD treatment significantly dampened the onset of inflammation in the livers and lungs and reduced the necroptosis and pyroptosis in livers. Moreover, CDK9 inhibition reduced inflammatory cytokine release and decreased cell death in the pro-inflammatory pyroptotic and necroptotic cell death pathway in monocytes in responses to lipopolysaccharide. In conclusion, CDK9 inhibition may affect the progress of endotoxemia by dampening inflammation and cell death including necroptosis and pyroptosis.

10.
Prog Biophys Mol Biol ; 155: 20-28, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32311424

RESUMEN

Cell survival or death is one critical issue in inflammatory responses. Ferroptosis, which is characterized by iron-dependent lethal lipid peroxidation, has been found to participate in the development of cancers, degenerative brain diseases and ischemia-reperfusion injuries. Incorporation of polyunsaturated fatty acids (PUFAs) into cellular membranes represents a vulnerability to invasion of microbials and sterile stimuli. In addition, the competition for iron in the battle between microbials and host cells underlies infection development. Although host cells have been equipped with complex antioxidant systems to combat lethal accumulation of lipid peroxidation, emerging evidence suggests several pathogens may target PUFAs in the cell membrane, and manipulate ferroptosis as a way for pathogen propagation. Moreover, ferroptosis takes part in the progression of sterile inflammations, such as cigarette smoke-induced chronic obstructive pulmonary disease, stroke and ischemia-reperfusion injuries. As iron-dependent oxidative stress and lipid peroxidation are common features for ferroptosis and inflammatory diseases, underlying mechanisms linking such pathological conditions will be discussed in this review. Progress in the research of ferroptosis may shed more light on the etiology and treatment of inflammatory diseases.

11.
Stem Cells Int ; 2020: 2016809, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32215014

RESUMEN

Most mesenchymal stem cells reside in a niche of low oxygen tension. Iron-chelating agents such as CoCl2 and deferoxamine have been utilized to mimic hypoxia and promote cell growth. The purpose of the present study was to explore whether a supplement of succinate, a natural metabolite of the tricarboxylic acid (TCA) cycle, can mimic hypoxia condition to promote human periodontal ligament cells (hPDLCs). Culturing hPDLCs in hypoxia condition promoted cell proliferation, migration, and osteogenic differentiation; moreover, hypoxia shifted cell metabolism from oxidative phosphorylation to glycolysis with accumulation of succinate in the cytosol and its release into culture supernatants. The succinate supplement enhanced hPDLC proliferation, migration, and osteogenesis with decreased succinate dehydrogenase (SDH) expression and activity, as well as increased hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), suggesting metabolic reprogramming from oxidative phosphorylation to glycolysis in a normal oxygen condition. The succinate supplement in cell cultures promoted intracellular succinate accumulation while stabilizing hypoxia inducible factor-1α (HIF-1α), leading to a state of pseudohypoxia. Moreover, we demonstrate that hypoxia-induced proliferation was G-protein-coupled receptor 91- (GPR91-) dependent, while exogenous succinate-elicited proliferation involved the GPR91-dependent and GPR91-independent pathway. In conclusion, the succinate supplement altered cell metabolism in hPDLCs, induced a pseudohypoxia condition, and enhanced proliferation, migration, and osteogenesis of mesenchymal stem cells in vitro.

12.
Biochem Biophys Res Commun ; 522(1): 184-190, 2020 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-31757417

RESUMEN

Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH-HIF-1α axis may facilitate host modulation therapy of chronic periodontitis.


Asunto(s)
Infecciones por Bacteroidaceae/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ligamento Periodontal/metabolismo , Periodontitis/metabolismo , Porphyromonas gingivalis/fisiología , Succinato Deshidrogenasa/metabolismo , Infecciones por Bacteroidaceae/microbiología , Células Cultivadas , Glucólisis , Interacciones Huésped-Patógeno , Humanos , Inflamación/metabolismo , Inflamación/microbiología , Fosforilación Oxidativa , Ligamento Periodontal/citología , Ligamento Periodontal/microbiología , Periodontitis/microbiología , Transducción de Señal , Ácido Succínico/metabolismo
13.
Stem Cell Res Ther ; 10(1): 320, 2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31730019

RESUMEN

BACKGROUND: The inflammation and regeneration process may be accompanied by the shift in the M1/M2 polarization of macrophages to adapt to extracellular signals. How the macrophages responded to the altered immunological environment in the periodontal niche after stem cell transplantation has never been explored. The purpose of present study is to investigate whether M1/M2 polarization of macrophages participated in the tissue homeostasis and wound healing during periodontal ligament stem cell (PDLSC)-based periodontal regeneration. METHODS: A rat periodontal defect model was utilized to observe the regeneration process in the PDLSC transplantation-enhanced periodontal repair. Dynamic changes in the markers of M1/M2 macrophages were observed on days 3, 7, and 21 post surgery. In addition, the outcome of regeneration was analyzed on day 21 after surgery. To further investigate the effect of PDLSCs on macrophage polarization, the conditioned medium of PDLSCs was utilized to treat M0, M1, and M2 macrophages for 24 h; markers of M1/M2 polarization were evaluated in macrophages. RESULTS: Elevated bone volume and average thickness of bone trabecular was observed in the PDLSC-treated group by micro-computed tomography on day 21. In addition, enhanced periodontal regeneration was observed in the PDLSC-treated group with cementum-like structure regeneration and collagen fiber formation, which inserted into the newly formed cementum. On day 3, PDLSC transplantation increased IL-10 level in the periodontal tissue, while decreased TNF-α in the early stage of periodontal regeneration. On day 7, enhanced CD163+ cell infiltration and heightened expression of markers of M2 macrophages were observed. Furthermore, conditioned medium from PDLSC culture induced macrophage polarization towards the anti-inflammatory phenotype by downregulating TNF-α and upregulating IL-10, Arg-1, and CD163 in vitro. CONCLUSIONS: PDLSCs could induce macrophage polarization towards the M2 phenotype, and the shift in the polarization towards M2 macrophages in the early stage of tissue repair contributed to the enhanced periodontal regeneration after stem cell transplantation. Therefore, signals from the transplanted PDLSCs might alter the immune microenvironment to enhance periodontal regeneration.


Asunto(s)
Polaridad Celular , Macrófagos/citología , Ligamento Periodontal/citología , Ligamento Periodontal/fisiología , Regeneración/fisiología , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Recuento de Células , Polaridad Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Citocinas/metabolismo , Interferón gamma/farmacología , Interleucina-4/farmacología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Masculino , Comunicación Paracrina/efectos de los fármacos , Ratas Sprague-Dawley , Receptores de Superficie Celular/metabolismo , Regeneración/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos
14.
Sci Rep ; 9(1): 17369, 2019 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-31758083

RESUMEN

Cyclin-dependent kinase 9 (CDK9), one crucial molecule in promoting the transition from transcription pausing to elongation, is a critical modulator of cell survival and death. However, the pathological function of CDK9 in bacterial inflammatory diseases has never been explored. CDK9 inhibition or knock-down attenuated Porphyromonas gingivalis-triggered inflammatory gene expression. Gene-expression microarray analysis of monocytes revealed that knock-down of CDK9 not only affected inflammatory responses, but also impacted cell death network, especially the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase domain-like (MLKL)-mediated necroptosis after P. gingivalis infection. Inhibition of CDK9 significantly decreased necroptosis with downregulation of both MLKL and phosphorylated MLKL. By regulating caspase-8 and cellular FLICE inhibitory protein (cFLIP), key molecules in regulating cell survival and death, CDK9 affected not only the classic RIPK1-RIPK3-mediated necroptosis, but also the alternate TIR-domain-containing adapter-inducing interferon-ß-RIPK3-mediated necroptosis. CDK9 inhibition dampened pro-inflammatory gene production in the acute infection process in the subcutaneous chamber model in vivo. Moreover, CDK9 inhibition contributed to the decreased periodontal bone loss and inflammatory response induced by P. gingivalis in the periodontal micro-environment. In conclusion, by modulating the RIPK3-MLKL-mediated necroptosis, CDK9 inhibition provided a novel mechanism to impact the progress of bacterial infection in the periodontal milieu.


Asunto(s)
Quinasa 9 Dependiente de la Ciclina/fisiología , Necroptosis/genética , Periodontitis/genética , Proteínas Quinasas/fisiología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/fisiología , Adulto , Animales , Infecciones por Bacteroidaceae/complicaciones , Infecciones por Bacteroidaceae/genética , Infecciones por Bacteroidaceae/metabolismo , Infecciones por Bacteroidaceae/patología , Estudios de Casos y Controles , Quinasa 9 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 9 Dependiente de la Ciclina/metabolismo , Progresión de la Enfermedad , Inhibidores Enzimáticos/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Periodontitis/metabolismo , Periodontitis/microbiología , Periodontitis/patología , Porphyromonas gingivalis/fisiología , Proteínas Quinasas/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Células THP-1 , Elongación de la Transcripción Genética/efectos de los fármacos
16.
J Oral Rehabil ; 46(8): 756-764, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30993704

RESUMEN

OBJECTIVES: The purpose of this study was to investigate whether a novel in situ interdental bone elevation method could achieve vertical bone augmentation around natural teeth. METHODS: Horizontal periodontal bone defects were created at nine quadrants of mandibles in five dogs. Six weeks later, one of the nine quadrants was randomly chosen as the model control. The remaining mandibles were allocated into two experimental groups: cortical bone removing (CBR) or interdental bone elevation (IBE). For the IBE group, four millimetres of interdental bone blocks were separated and elevated from the base of alveolar bone. Then bone xenografts were implanted beneath the elevated alveolar blocks. Animals were euthanised 12 weeks post-operation. Cone beam computed tomography (CBCT) examination and histological analysis were performed to evaluate the surgical outcomes. RESULTS: Enhanced soft tissue profiles were observed in the two experimental groups as compared to the model control group. CBCT images showed that the height of alveolar bone was significantly higher in the IBE group with bone blocks seated near the cementoenamel junction. Significantly larger area of bone tissues with the highest coronal level of new bone was observed in the IBE group. New bone was observed around the elevated bone blocks with bone remodelling and neovascularisation inside the elevated blocks. CONCLUSIONS: Vertical bone augmentation at interdental sites may be performed through in situ interdental bone elevation for patients with horizontal alveolar bone resorption.


Asunto(s)
Pérdida de Hueso Alveolar , Animales , Tomografía Computarizada de Haz Cónico , Perros , Humanos , Mandíbula , Proyectos Piloto
17.
J Orthod Sci ; 7: 13, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29963508

RESUMEN

OBJECTIVES: This study was designed to explore whether force magnitude would influence incisor torque control and the overall outcome in patients with bimaxillary protrusion who need mass incisor retraction. MATERIALS AND METHODS: Forty-one female patients (aged > 15 years) with bimaxillary protrusion requiring mass incisor retraction were selected. Two sliding mechanics were utilized, with the elastic group receiving a light force of ~100 g by wearing elastics and the power chain group receiving a moderate force of ~250 g by power chain. Lateral cephalograms obtained before and after treatment were traced and measured. RESULTS: Patients in both groups displayed maxillary protrusion with a similar skeletal class II tendency. A longer treatment time was found in the elastic group. No difference in the distance of incisor tip movement was observed between the two groups; however, a larger inclination of upper incisors was found in the elastic group, indicating less loss of torque. In addition, larger reduction in Sella-Nasion-A and A-Nasion-B angle was observed in the elastic group, which was accompanied by a larger ratio of upper lip retraction to upper incisor retraction as well as more upper lip retraction. CONCLUSIONS: Sliding mechanics with elastics to generate light forces can achieve better torque control with more reduction in skeletal and soft tissue protrusion.

18.
Medicine (Baltimore) ; 97(20): e10707, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29768336

RESUMEN

RATIONALE: Lymphomas are the second most common non-epithelial malignant tumors in the oral and maxillofacial region. Non-Hodgkin's lymphoma (NHL) develops at extranodal sites, and cases involving the maxilla account for less than 1% of all NHLs. We describe a case of diffuse large B-cell lymphoma (DLBCL) in the maxilla, and highlight the clinical signs, symptoms, differential diagnosis, and appropriate treatment of DLBCL in the oral cavity and maxillofacial region. PATIENT CONCERNS: A 67-year-old woman was admitted to our surgical department with pain and swelling in her right upper posterior teeth for about six months. She was previously misdiagnosed with periodontal disease and had a history of tooth extraction. DIAGNOSES: Computed tomography (CT) scan revealed extensive osteolysis in the right posterior part of the maxilla with enhanced neoplasm. A solid mass was found upon incisional biopsy, and immunohistochemistry confirmed the diagnosis of DLBCL. INTERVENTIONS: The patient was treated with six courses of rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone (R-CHOP), followed by external irradiation treatment. OUTCOMES: The treatment was well tolerated, and the patient is presently alive after two years of follow-up. LESSONS: Non-specific symptoms, such as unclear primary dental pain and unresolved periapical swelling, can make an accurate diagnosis of DLBCL difficult, which frequently lead to delayed diagnosis. A CT or cone beam computed tomography (CBCT) scan of the maxilla and immunohistochemical staining of the biopsy specimen is recommended. Combination therapy including radiotherapy and chemotherapy is the optimal treatment for NHL.


Asunto(s)
Linfoma de Células B Grandes Difuso/diagnóstico , Maxilar/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Ciclofosfamida/uso terapéutico , Diagnóstico Diferencial , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células B Grandes Difuso/terapia , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Tomografía Computarizada por Rayos X , Vincristina/uso terapéutico
19.
Biomed Pharmacother ; 95: 1187-1193, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28931210

RESUMEN

OBJECTIVE: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 1(PCAT-1) has been shown to be dysregulated and exert vital roles in tumorigenesis and progression of various malignancies. However, the precise molecular mechanism in the metastasis and invasion of HCC remain unclear. METHODS: The expression levels of PCAT1 derived from human HCC tissues and cell lines were analyzed through quantitative real-time PCR. QRT-PCR was also applied to detect the expression of HMGB1 and miR-129-5p. Wound healing assay and transwell assays were performed to analyze cell migration and invasion ability. The mRNA levels and protein expression of HMGB1 were detected by western-blotting analysis and immunohistochemistry, respectively. Luciferase assays were used to investigate binding seeds beteen miRNA-129-5p and other transcripts, such as PCAT-1, HMGB1. RESULT: In this study, our founding demonstrated that PCAT-1 was not only aberrantly upregulated in HCC tissues and cell lines, but also associated with TNM stage, metastasis and Histological grade. In vitro, downregulation of PCAT-1 could reduce the invasion and migration of HCC cells. Moreover, our results showed that PCAT-1 could act as an endogenous RNA by directly binding to miR-129-5p. In addition, Luciferase reporter assay and western blotting analyses showed that PCAT-1 repressed inhibitory effect of miR-129-5p and reverse high mobility group box 1 (HMGB1) expression, a target gene of miR-129-5p. CONCLUSION: PCAT-1 functions as competing endogenous RNA (ceRNA) to provide a better understanding for HCC metastasis, and serves as a potential diagnostic and therapeutic target via PCAT-1/miR-129-5p/HMGB1 regulatory crosstalk for the deadly disease.


Asunto(s)
Carcinoma Hepatocelular/genética , Proteína HMGB1/metabolismo , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Transducción de Señal , Secuencia de Bases , Carcinoma Hepatocelular/patología , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , ARN Largo no Codificante/genética , Regulación hacia Arriba/genética
20.
Mol Immunol ; 91: 65-74, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28886588

RESUMEN

Human ß-defensin 3 (hBD3) is a cationic peptide with immunomodulatory effects on both innate and acquired immune responses. Periodontitis, an inflammatory disease that extends deep into periodontal tissues, causes the loss of supporting structures around the tooth. The present study assessed the effects of hBD3 as a monotherapy for periodontitis in mice and explored its potential mechanism. In vivo, hBD3 inhibited the levels of tumour necrosis factor (TNF)-α, interleukin-6, and matrix metalloprotease-9 in periodontium exposed to Porphyromonas gingivalis (P.g) in a mouse periodontitis model; reduced osteoclast formation and lower alveolar bone loss were also observed. In addition, hBD3 was related to the expression of polarization signature molecules in circulating monocytes. In vitro, hBD3 notably suppressed the production of TNF-α and interleukin-6 in RAW 264.7 cells stimulated by the lipopolysaccharide of P.g. Moreover, hBD3 attenuated polarization of RAW 264.7 cells into the M1 phenotype, with reduced activation of nuclear factor-κB signal transduction. In conclusion, hBD3 exhibits potent anti-periodontitis properties both in vitro and in vivo, and this effect may be correlated to inhibition of the nuclear factor-κB pathway and macrophage polarization.


Asunto(s)
Pérdida de Hueso Alveolar/inmunología , Infecciones por Bacteroidaceae/inmunología , Osteoclastos/inmunología , Periodontitis/inmunología , Porphyromonas gingivalis/inmunología , beta-Defensinas/farmacología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/genética , Pérdida de Hueso Alveolar/patología , Animales , Infecciones por Bacteroidaceae/tratamiento farmacológico , Infecciones por Bacteroidaceae/genética , Infecciones por Bacteroidaceae/patología , Modelos Animales de Enfermedad , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Noqueados , Osteoclastos/patología , Periodontitis/tratamiento farmacológico , Periodontitis/genética , Periodontitis/patología , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
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