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1.
Arch Oral Biol ; 109: 104588, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669922

RESUMO

OBJECTIVE: Dental occlusion are frequently changed in clinic. Molecular responses in jaw muscles to aberrant dental occlusion are changes are attractive, yet remain are obscure. DESIGN: Unilateral anterior crossbite (UAC) prostheses were applied to Sprague-Dawley rats and then ceased after two weeks to detect the reactions of the masseter, a representative jaw elevator, and the lateral pterygoid muscle (LPM), a representative jaw depressor. RESULTS: Two weeks of UAC elicited mild injury of the two muscles. Myogenesis and protective reactions were detected as increases in αB-crystallin expression in the masseter after 3 days and in the LPM after 2 weeks, and increases in desmin expression in both muscles after 2 weeks. A switch in fibre types from IIb to IIx occurred in the LPM but not in the masseter. Inflammatory responses, shown by the infiltration of inflammatory cells and increases in TNF-α mRNA expression, and fibrosis responses, shown by increased mRNA expression of Type I and III collagens, appeared very mild in the two muscles. These responses were partially recovered by the cessation of UAC. During the whole process, no obvious changes were observed in mitochondrial function, as indicated by the levels of proliferator-activated receptor γ coactivator 1α, mitofusin-2 and voltage-dependent anion channel. CONCLUSIONS: UAC causes injury and very limited inflammatory and fibrosis adaption in the masseter and LPM. Both muscles respond with myogenesis and protective activity. The LPM responds also with muscle fibre isoform alternations. These alterations were partially recovered by the cessation of dental stimulation at an early stage.


Assuntos
Implantes Dentários/efeitos adversos , Má Oclusão , Músculo Masseter/fisiopatologia , Músculos Pterigoides/fisiopatologia , Animais , Fibrose , Inflamação , Arcada Osseodentária , Músculo Masseter/lesões , Fibras Musculares Esqueléticas , Músculos Pterigoides/lesões , Ratos , Ratos Sprague-Dawley
2.
Oral Dis ; 25(7): 1759-1768, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357246

RESUMO

OBJECTIVES: To detect whether early growth response 1 (EGR1) in peripheral blood leucocytes (PBLs) indicates temporomandibular joint (TMJ) osteoarthritis (OA) lesions. MATERIALS AND METHODS: Egr1 mRNA expression levels in PBLs were detected in eight malocclusion patients without temporomandibular disorder (TMD) signs and 16 malocclusion patients with clinical TMD signs with (eight) or without (eight) imaging signs of TMJ OA. Twelve 6-week-old rats were randomized to a control group and a unilateral anterior crossbite (UAC) group and were sampled at 4 weeks. The Egr1 mRNA expression levels in PBLs and protein expression levels in different orofacial tissues were measured. RESULTS: Patients with TMD signs with/without TMJ OA diagnosis showed lower Egr1 mRNA expression levels in PBLs than patients without TMD signs. The lower Egr1 mRNA expression was also found in the PBLs of UAC rats, which were induced to exhibit early histo-morphological signs of TMJ OA lesions. In subchondral bone of UAC rats, EGR1 protein expression was decreased, co-localization of EGR1 with osterix or dentin matrix protein-1 was identified, and the number of EGR1 and osterix double-positive cells was reduced (all p < .05). CONCLUSION: Egr1 reduction in PBLs potentially indicates subchondral bone OA lesions at an early stage.

3.
J Oral Rehabil ; 46(9): 820-827, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31046158

RESUMO

Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty-four six-week-old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene-fold changes in PBLs were detected by a microarray analysis comparing rats that received 20-week unilateral anterior crossbite (UAC) treatment with age-matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA-like lesions. The other twenty-four rats were randomly placed in the UAC and control groups at 12- and 20-week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real-time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1-positive, EXPH1-positive and IL10-positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation.


Assuntos
Cartilagem Articular , Transtornos da Articulação Temporomandibular , Animais , Côndilo Mandibular , Ratos , Ratos Sprague-Dawley , Articulação Temporomandibular
4.
Oral Dis ; 25(6): 1589-1599, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132303

RESUMO

OBJECTIVE: We aimed to develop a mouse model predominating in a proliferative response in the articular cartilage of the temporomandibular joints. MATERIALS AND METHODS: Bilateral anterior elevation of occlusion was developed by installing metal tubes onto the incisors of mice with edge-to-edge relation to prevent tooth wear, leading to an increase in the vertical height of the dental occlusion with time. Morphological changes and expression changes in Cyclin D1, Aggrecan, and type II and type X collagen in the mandibular condylar cartilage were detected. In addition, cells were isolated from the mandibular condylar cartilage and exposed to cyclic tensile strain (CTS). RESULTS: Compared with age-matched controls, the tooth length was longer at 3 weeks, 7 weeks, and 11 weeks in BAE mice (p < 0.05), with increased condylar cartilage thickness, matrix amount, and cell number (p < 0.05). Compared with the deep zone cells, CTS stimulated the superficial zone cells to express a higher level of proliferating cell nuclear antigen, Cyclin D1, Aggrecan, and type II collagen but a lower level of type X collagen and alkaline phosphatase. CONCLUSION: Bilateral anterior elevation stimulated the proliferative response in the mandibular condylar cartilage, offering a new therapeutic strategy for cartilage degeneration.

5.
Am J Chin Med ; 47(3): 577-594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30974967

RESUMO

Thymoquinone (TQ) is a main aromatic component of Nigella sativa L. seeds or Agastache rugosa (Fisch. & C.A.Mey.) Kuntze. The protective mechanism of TQ against acute liver injury induced by acetaminophen (APAP), however, remains unclear. We aimed to investigated the hepato-protective mechanism of TQ on the development of APAP-induced acute liver injury. Male kunming mice were pretreated with TQ or N-acetylcysteine (NAC) before a single APAP injection. Human Chang liver cells were incubated with TQ, SP600125 or AICAR in presence of APAP for 24 h. TQ pretreatment reduced levels of serum aminotransferases and increased hepatic glutathione and glutathione peroxidase activities via inhibiting CYP2E1 expression. TQ inhibited JNK, ERK and P38 phosphorylation induced by APAP. Meanwhile, TQ inhibited PI3K/mTOR signaling activation and activated AMPK phosphorylation. Moreover, TQ prevented APAP-induced hepatocytes apoptosis regulated by Bcl-2 and Bax. Furthermore, TQ inhibited STAT3 phosphorylation on APAP-induced acute liver injury. In addition, TQ significantly inhibited P2X7R protein expression and IL-1 ß release. APAP-enhanced JNK phosphorylation and APAP-suppressed AMPK phosphorylation were also observed in Chang liver cells, and these changes were recovered by pretreatment with TQ, SP600125 and AICAR. Our findings suggest that TQ may actively prevent APAP-induced acute liver injury, and the effect may be mediated by JNK and AMPK signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Benzoquinonas/farmacologia , Benzoquinonas/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Overdose de Drogas/complicações , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fitoterapia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Hepatócitos/efeitos dos fármacos , Humanos , Inflamação , Masculino , Camundongos
6.
J Oral Rehabil ; 46(4): 340-348, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30556174

RESUMO

BACKGROUND: The temporomandibular joint (TMJ) disc plays a role in joint movement and in load absorbance and distribution. An experimental unilateral anterior crossbite (UAC) prosthesis induces mandibular condylar cartilage degeneration in rats. However, the changes in the articular disc are still unknown. OBJECTIVE: To describe changes in the TMJ discs of UAC rats. METHODS: The discs of fifty-four Sprague-Dawley rats, equally distributed into a UAC group and an age-matched sham-operated control group at 4, 12 and 20 weeks (n = 9), were evaluated by gross and histomorphological observation and by detection at the mRNA or protein expression levels of the markers related to the matrix elements. RESULTS: No macro- or micro-morphological differences were observed between groups. However, there were catabolic degradative changes at the molecular level in the UAC group, showing a significant reduction in the mRNA and/or protein expression levels of many molecules. The reduction became worse with time (P < 0.05). The reduced molecules included: (a) those related to the extracellular matrix, such as type I collagen, decorin and fibromodulin; (b) those related to chondrogenesis, such as type II collagen and aggrecan; and (c) those related to osteogenesis, such as alkaline phosphatase and runt-related transcription factor 2. The mRNA expression of vascular endothelial growth factor did not change. In contrast, fibronectin, which can promote wound healing, and its N-terminal fragment, which can induce cartilage degradation, were accumulated (P < 0.05). CONCLUSION: TMJ discs were stimulated to catabolic changes by the aberrant dental occlusion and seemed to go to inanimate with time.


Assuntos
Má Oclusão/metabolismo , Má Oclusão/patologia , Côndilo Mandibular/metabolismo , Côndilo Mandibular/patologia , Disco da Articulação Temporomandibular/metabolismo , Disco da Articulação Temporomandibular/patologia , Animais , Cartilagem Articular/patologia , Condrócitos/patologia , Oclusão Dentária , Modelos Animais de Doenças , Feminino , Má Oclusão/complicações , Fenômenos Mecânicos , Ratos , Ratos Sprague-Dawley
7.
J Agric Food Chem ; 66(50): 13183-13190, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30497264

RESUMO

Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol-feeding murine models were established by intragastrically administering ethanol or feeding an ethanol-containing Lieber-DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG), and hepatic TG levels. Hematoxylin and eosin (HE) and Oil Red O staining confirmed that P. citrinopileatus ameliorated both acute and chronic alcoholic hepatosteatosis, characterized by regulation of lipid-metabolism-related proteins, including sirtuin 1 (SIRT1), AMP-activated kinase (AMPK), and sterol regulatory element-binding protein (SREBP1). P. citrinopileatus reversed inflammatory response via modulating purinergic receptor P2X ligand-gated ion channel 7 (P2X7R)-NOD-like receptor pyrin domain 3 (NLRP3) inflammasome. P. citrinopileatus restored the expressions of those proteins to a normal level. In addition, HepG2 cells were incubated with P. citrinopileatus prior to ethanol stimulation. P. citrinopileatus reduced ethanol exposure-induced lipid deposition. Concomitantly, P. citrinopileatus increased AMPK and SIRT1 expressions, which were reduced by ethanol treatment. P. citrinopileatus ameliorated alcoholic hepatic steatosis and accompanied inflammatory response via regulating SIRT1-AMPK and P2X7R-NLRP3 inflammasome activation, highlighting a promising strategy and utility of P. citrinopileatus for alcoholic steatohepatitis as dietary health supplements.


Assuntos
Fígado Gorduroso Alcoólico/tratamento farmacológico , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Pleurotus/química , Receptores Purinérgicos P2X7/imunologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/imunologia , Animais , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/imunologia , Fígado Gorduroso Alcoólico/metabolismo , Células Hep G2 , Humanos , Inflamassomos/genética , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Receptores Purinérgicos P2X7/genética , Sirtuína 1/genética , Sirtuína 1/imunologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/imunologia , Triglicerídeos/metabolismo
8.
Neuroscience ; 340: 445-454, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-27865869

RESUMO

This study was to investigate the role of p38 activation via ERK1/2 phosphorylation in neurons and microglia of the spinal trigeminal subnucleus caudalis (Vc) in the promotion of orofacial hyperalgesia induced by unilateral anterior crossbite (UAC) traumatic occlusion in adult rats. U0126, a p-ERK1/2 inhibitor, was injected intracisternally before UAC implant. The effects of the U0126 injection were compared to those following the injection of SB203580, a p-p38 inhibitor. Mechanical hyperalgesia was evaluated via pressure pain threshold measurements. Brain stem tissues were processed for a Western blot analysis to evaluate the activation of ERK1/2 and p38. Double immunofluorescence was also performed to observe the expression of p-ERK1/2 and p-p38 in neurons (labeled by NeuN) and microglia (labeled by OX42). The data showed that UAC caused orofacial hyperalgia ipsilaterally on d1 to d7, peaking on d3 (P<0.05). An upregulation of p-ERK1/2 was observed in the ipsilateral Vc on d1 to d3, peaking on d1. An upregulation of p-p38 was also observed on d1 to d7, peaking on d3 (P<0.05). p-ERK1/2 primarily co-localized with NeuN and, to a lesser extent, with OX42, while p-p38 co-localized with both NeuN and OX42. Pretreatment with U0126 prevented the upregulation of both p-ERK1/2 and p-p38. Similarly to an intracisternal injection of SB203580, U0126 pretreatment attenuated the UAC-induced orofacial hyperalgesia. These data indicate that UAC caused orofacial hyperalgesia by inducing central sensitization via the activation of ERK1/2 and p38 in both neurons and microglia in the Vc, potentially impacting the effects of p-ERK1/2 during p38 activation.


Assuntos
Sensibilização do Sistema Nervoso Central/fisiologia , Dor Facial/enzimologia , Hiperalgesia/enzimologia , Sistema de Sinalização das MAP Quinases/fisiologia , Núcleo Espinal do Trigêmeo/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Modelos Animais de Doenças , Dor Facial/patologia , Feminino , Hiperalgesia/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/enzimologia , Microglia/patologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/patologia , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Fosforilação , Distribuição Aleatória , Ratos Sprague-Dawley , Núcleo Espinal do Trigêmeo/efeitos dos fármacos , Núcleo Espinal do Trigêmeo/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
9.
Sci Rep ; 6: 30085, 2016 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-27452863

RESUMO

This study tested whether activation of adrenoreceptors in chondrocytes has roles in degenerative remodelling of temporomandibular joint (TMJ) and to determine associated mechanisms. Unilateral anterior crossbite (UAC) was established to induce TMJ degeneration in rats. Saline vehicle, α2- and ß-adrenoreceptor antagonists or agonists were injected locally into the TMJ area of UAC rats. Cartilage degeneration, subchondral bone microarchitecture and the expression of adrenoreceptors, aggrecans, matrix metalloproteinases (MMPs) and RANKL by chondrocytes were evaluated. Chondrocytes were stimulated by norepinephrine to investigate signal transduction of adrenoreceptors. Increased α2A-adrenoreceptor expression was observed in condylar cartilage of UAC rats, together with cartilage degeneration and subchondral bone loss. Norepinephrine depresses aggrecans expression but stimulates MMP-3, MMP-13 and RANKL production by chondrocytes through ERK1/2 and PKA pathway; these effects were abolished by an α2A-adrenoreceptor antagonist. Furthermore, inhibition of α2A-adrenoreceptor attenuated degenerative remodelling in the condylar cartilage and subchondral bone, as revealed by increased cartilage thickness, proteoglycans and aggrecan expression, and decreased MMP-3, MMP-13 and RANKL expressions in cartilage, increased BMD, BV/TV, and decreased Tb.Sp in subchondral bone. Conversely, activation of α2A-adrenoreceptor intensified aforementioned degenerative changes in UAC rats. It is concluded that activation of α2A-adrenergic signal in chondrocytes promotes TMJ degenerative remodelling by chondrocyte-mediated pro-catabolic activities.


Assuntos
Condrócitos/metabolismo , Osteoartrite/patologia , Receptores Adrenérgicos alfa 2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/patologia , Agonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/farmacologia , Agrecanas/biossíntese , Animais , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Feminino , Côndilo Mandibular/fisiologia , Metaloproteinases da Matriz/biossíntese , Norepinefrina/farmacologia , Ligante RANK/biossíntese , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos beta/biossíntese , Articulação Temporomandibular/citologia
10.
J Phys Chem B ; 118(45): 12972-8, 2014 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-25350322

RESUMO

With the use of isothermogravimetrical analysis, the enthalpies of vaporization, Δ(g)lH(o)m(T(av)), at the average temperature, T(av) = 445.65 K, for the ionic liquids (ILs) 1-alkyl-3-methylimidazolium propionate [C(n)mim][Pro](n = 4, 5, 6) were determined. Using Verevkin's method, the difference of heat capacities between the vapor phase and the liquid phase, Δ(g)lC(p)(o)m, for [C(n)mim][Pro](n = 2, 3, 4, 5, 6), were calculated based on the statistical thermodynamics. Therefore, with the use of Δ(g)lC(p)(o)m, the values of Δ(g)lH(o)m(T(av)) were transformed into Δ(g)lH(o)m(298), 126.8, 130.3, and 136.5 for [C(n)mim][Pro](n = 4, 5, 6), respectively. In terms of the new scale of polarity for ILs, the order of the polarity of [C(n)mim][Pro](n = 2, 3, 4, 5, 6) was predicted, that is, the polarity decreases with increasing methylene. A new model of the relationship between the surface tension and the enthalpy of vaporization for aprotic ILs was put forward and used to predict the surface tension for [C(n)mim][Pro](n = 2, 3, 4, 5, 6) and others. The predicted surface tension for the ILs is in good agreement with the experimental one.

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