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BACKGROUND: High serum NEFA and GDF-15 are risk factors for CAD and have been linked to detrimental cardiovascular events. It has been hypothesized that hyperuricemia causes CAD via the oxidative metabolism and inflammation. The current study sought to clarify the relationship between serum GDF-15/NEFA and CAD in individuals with hyperuricemia. METHODS: Blood samples collected from 350 male patients with hyperuricemia(191 patients without CAD and 159 patients with CAD, serum UA > 420 µmol/L) to measure serum GDF-15 and NEFA concentrations with baseline parameters. RESULTS: Serum circulating GDF-15 concentrations(pg/dL) [8.48(6.67,12.73)] and NEFA levels(mmol/L) [0.45(0.32,0.60)] were higher in hyperuricemia patients with CAD. Logistic regression analysis revealed that the OR (95% CI) for CAD were 10.476 (4.158, 26.391) and 11.244 (4.740, 26.669) in quartile 4 (highest) respectively. The AUC of the combined serum GDF-15 and NEFA was 0.813 (0.767,0.858) as a predictor of whether CAD occurred in male with hyperuricemia. CONCLUSIONS: Circulating GDF-15 and NEFA levels correlated positively with CAD in male patients with hyperuricemia and measurements may be a useful clinical adjunct.
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Enfermedad de la Arteria Coronaria , Hiperuricemia , Humanos , Masculino , Factor 15 de Diferenciación de Crecimiento , Ácidos Grasos no Esterificados , Hiperuricemia/complicaciones , InflamaciónRESUMEN
AIMS: Epidemiological studies consistently show that decreases in serum testosterone level are observed more frequently in men with type 2 diabetes mellitus (T2DM), while clinical investigations have demonstrated that an increased level of circulating growth differentiation factor-15 (GDF-15) are also related closely to T2DM. The aim of this study was to examine the potential relationship between serum GDF-15 levels and hypogonadism in Chinese male patients with T2DM. MATERIALS AND METHODS: A total of 305 T2DM men were recruited between July 2020 and August 2021. GDF-15 and total testosterone concentrations were quantified by an enzyme-linked immunosorbent assay and LC/MS mass spectrometry, respectively. Multiple linear regression analysis, logistic regression, and restricted cubic splined models were used to examine the correlation between GDF-15 levels and hypogonadism in these patients. RESULTS: When compared with T2DM patients without hypogonadism circulating GDF-15 levels were significantly higher in the hypogonadism group [1081.83 (746.79,1539.94) versus 779.49 (548.46,1001.27), p < 0.001] and were associated positively with hypogonadism in unadjusted and fully adjusted multivariate regression models (p < 0.01). The fully adjusted regression coefficients with 95% confidence intervals for circulating GDF-15 and testosterone deficiency were -1.795 (-2.929, -0.661). Serum GDF-15 levels were also associated positively with testosterone deficiency in each logistic regression model (p < 0.05), while after adjustment for all risk factors, the same findings were obtained in the restricted cubic splined models (p < 0.01). CONCLUSIONS: In hypogonadal men with T2DM, an elevated serum GDF-15 level is associated negatively with serum testosterone concentration. GDF-15 may be a novel cytokine related to T2DM men with hypogonadism.
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Diabetes Mellitus Tipo 2 , Hipogonadismo , Diabetes Mellitus Tipo 2/complicaciones , Factor 15 de Diferenciación de Crecimiento , Humanos , Hipogonadismo/complicaciones , Masculino , Factores de Riesgo , TestosteronaRESUMEN
BACKGROUND: Clinical investigations have found that there was a close association between T2DM and adverse cardiovascular events, with possible mechanisms included inflammation, apoptosis, and lipid metabolism disorders. High serum GDF-15 concentration and the apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) are involved in the above-mentioned mechanisms and are thought to be related to the occurrence of adverse cardiovascular events. However, it remains unclear whether circulating GDF-15 levels and the ApoB/ApoA1 ratio are related to T2DM patients with CAD. METHODS: T2DM patients with or without CAD were eligible for this study. According to the inclusion and exclusion criteria, 502 T2DM patients were enrolled between January 2021 and December 2021 and were then divided into T2DM group (n = 249) and CAD group (n = 253). The ApoB, ApoA1 and GDF-15 concentrations were measured at hospital admission and the ApoB/ApoA1 ratio was then calculated. RESULTS: Compared with T2DM group, serum GDF-15 levels and ApoB/ApoA1 ratio increased in CAD group. Furthermore, a positive relationship between the occurrence of CAD in diabetic population and circulating GDF-15 concentrations and ApoB/ApoA1 ratio was observed in logistic regression analysis (p < 0.01). Restrictive cubic spline analysis after adjusted for multiple risky variables showed that serum GDF-15 or ApoB/ApoA1 ratio correlated positively with CAD. CONCLUSIONS: Circulating GDF-15 levels and serum ApoB/ApoA1 ratio vary in CAD group and T2DM group. ApoB/ApoA1 and GDF-15 may be helpful for predicting the occurrence of CAD in patients with T2DM.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Apolipoproteína A-I , Apolipoproteína B-100 , Apolipoproteínas B , Biomarcadores , Diabetes Mellitus Tipo 2/complicaciones , Factor 15 de Diferenciación de Crecimiento , HumanosRESUMEN
OBJECTIVE: This retrospective study was purposed to evaluate epidemiological, clinical, and 3D radiological features of supernumerary teeth (ST) in a non-syndromic Chinese children and adolescent dental population. MATERIALS AND METHODS: Original cone-beam CT (CBCT) data from 18,861 patients aged from 6 to 17 years with dental maxillofacial diseases treated in a Chinese dental hospital from June 2012 to December 2018 were utilized to screen patients with ST. Diagnosis and characterizations of ST were analyzed by CBCT coupled with 3D reconstruction. All relevant epidemiological, clinical, and radiographic details about ST were collected and statistically analyzed. RESULTS: Among total 18,861 patients, 2,768 ST were identified in 1984 subjects with a prevalence of 10.52% and a male:female ratio of 1.86:1. Majority of ST were single, conical, inverted, impacted, and located in maxilla anterior region. ST-associated complications mainly included malposition, rotation, and impaction of adjacent teeth, which were notably associated with morphology and position of ST. CONCLUSION: The prevalence of ST in Chinese children and adolescent dental population was 10.52% and tended to present as single, conical, inverted, and impacted, which resulted in abnormalities of neighboring teeth. Our outcomes are beneficial for clinicians to more comprehensively understand the incidence, characterization, and clinical treatment planning of ST in dental children and adolescents.
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Diente Impactado , Diente Supernumerario , Adolescente , Anciano , Niño , China/epidemiología , Femenino , Humanos , Masculino , Maxilar , Estudios Retrospectivos , Diente Supernumerario/diagnóstico por imagen , Diente Supernumerario/epidemiologíaRESUMEN
BACKGROUND: Early childhood caries has been designated as a serious public health problem. The traditional restoration method is very challenging, especially in uncooperative patients. Non-invasive therapy, like remineralization agents, which have been developed to reverse the demineralization progress at the early stage of caries, may be a better choice. This study aimed to evaluate the remineralization efficacy of different concentrations of 45S5 bioactive glass (BAG) on artifical carious lesions of deciduous enamel. METHODS: 65 caries-like enamel lesions of the deciduous teeth were assigned to 5 groups (n = 13) and transported to a 14 days pH-cycling: Group A: 2%BAG, Group B: 4%BAG, Group C: 6%BAG, Group D: 8%BAG, and Group E: deionized water (DDW, negative control). 8 sound (Group F) and 8 demineralized teeth (Group G) were prepared for contrast. The recovery power of mechanical property was evaluated by Vickers hardness test through the recovery of enamel microhardness (%REMH). Surface morphology, mass fraction of Ca and P ions, and Ca/P atomic ratio were analyzed by scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (EDX). Moreover, Fourier transform infrared spectroscopy equipped with attenuated total reflectance was used to identify the chemical structure of newly formed compounds. RESULTS: % REMH were (42.65 ± 1.35), (52.59 ± 2.96), (57.40 ± 1.72), (52.91 ± 2.55), (12.46 ± 2.81) in 2%BAG, 4%BAG, 6%BAG, 8%BAG, and DDW groups respectively. Micro-spherical particles were deposited in all BAG groups and 6% BAG showed the densest and most uniform surface. EDX analysis identified significantly higher Ca(wt%) and P(wt%) in four BAG groups than in the demineralized group (p < 0.005), while 6% BAG showed the highest mineral gain efficacy. The infrared spectrum demonstrated that newly mineralized crystals were consisted of type-B hydroxycarbonate apatite. CONCLUSION: BAG possessed a promising remineralization effect on artificial lesions in deciduous enamel by recovering enamel surface mechanical property, morphology and chemical elements. Among them, 6% BAG performed the greatest overall efficacy. Acting as a new caries-arresting biomaterial, 45S5 BAG has the potential to facilitate the adaptation of better carious prevention strategies in children.
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Caries Dental , Remineralización Dental , Preescolar , Caries Dental/terapia , Esmalte Dental , Vidrio , Humanos , Diente PrimarioRESUMEN
Streptococcus mutans (S. mutans) is the principal etiologic agent in the occurrence of human dental caries and the formation of biofilms on the surface of teeth. Tea tree oil (TTO) has been demonstrated to exhibit a wide range of pharmacological actions that can effectively inhibit the activity of bacteria. In this context, we evaluated the in vitro antimicrobial effects of TTO on S. mutans both during planktonic growth and in biofilms compared with 0.2% CHX. We determined the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) using the microdilution method, the bacteriostatic rate using an MTT assay, and the antimicrobial time using a time-kill assay. Then, we explored the effects of TTO on acid production and cell integrity. Furthermore, the effects of TTO on the biomass and bacterial activity of S. mutans biofilms were studied. Finally, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to investigate the structure and activity of biofilms. The MIC and MBC values were 0.125% and 0.25%, and the bacterial inhibition rate was concentration dependent. TTO can effectively inhibit bacterial acid production and destroy the integrity of the cell membrane. Electron micrographs revealed a reduction in bacterial aggregation, inhibited biofilm formation, and reduced biofilm thickness. The effect of TTO was the same as that of 0.2% CHX at a specific concentration. In summary, we suggest that TTO is a potential anticariogenic agent that can be used against S. mutans.
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Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Aceite de Árbol de Té/farmacología , Caries Dental/microbiología , Humanos , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana , Microscopía Confocal , Microscopía Electrónica de Rastreo , Streptococcus mutans/efectos de los fármacosRESUMEN
OBJECTIVE: Given the intricate challenges and potential complications associated with periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH). Our study aimed to compare the clinical and imaging benefits and drawbacks of two surgical approaches, the modified Stoppa combined iliac spine approach and the modified Smith-Peterson approach, for treating PAO and to provide guidance for selecting clinical approaches. METHODS: A retrospective analysis of 56 patients with 62 DDHs was conducted from June 2018 to January 2022. The experimental group underwent surgery via the modified Stoppa combined iliac spine approach, while the control group underwent surgery via the modified Smith-Peterson approach for periacetabular osteotomy and internal fixation. Basic statistical parameters, including age, sex, BMI, and preoperative imaging data, were analyzed. Differences in surgical time, intraoperative blood loss, and postoperative imaging data were compared, as were differences in preoperative and postoperative imaging data between the two groups. RESULTS: There were 28 hips in the experimental group and 34 in the control group. Moreover, there was no significant difference in the basic parameters between the experimental and control groups. Before and after the operation, for the LCE angle, ACE angle, and Tonnis angle, there was no significant difference in acetabular coverage (p > 0.05). However, there were significant differences between the two groups in terms of the above four indicators before and after the operation (p < 0.05). After the operation, the experimental group exhibited significant increases in both lateral and anterior acetabular coverage of the femoral head. However, the experimental group had longer operation times and greater bleeding volumes than did the control group. Despite this, the experimental group demonstrated significant advantages in protecting the lateral femoral cutaneous nerve compared to the control group. CONCLUSION: The modified Stoppa combined iliac spine approach can be considered a practical approach for PAO and is more suitable for patients with DDH who plan to be treated by one operation than the classic modified Smith-Peterson approach for PAO.
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Acetábulo , Displasia del Desarrollo de la Cadera , Osteotomía , Humanos , Estudios Retrospectivos , Femenino , Osteotomía/métodos , Masculino , Displasia del Desarrollo de la Cadera/cirugía , Displasia del Desarrollo de la Cadera/diagnóstico por imagen , Adulto , Acetábulo/cirugía , Acetábulo/diagnóstico por imagen , Persona de Mediana Edad , Adulto Joven , AdolescenteRESUMEN
Osteoarthritis (OA) is a major cause of disability, characterized by chronic pain, irreversible destruction, and loss of function of the articular cartilage. The integrity and arrangement of the composition and structure of the extracellular matrix (ECM) are essential for maintaining the elasticity, integrity, and mechanical support function of the cartilage tissue. Osteoarthritis causes substantial changes in the ECM, driving the progression of the disease. Recent studies have shown that the ECM plays a critical role in the development of cartilage tissue as well as the occurrence and development of osteoarthritis by directly or indirectly regulating chondrocyte proliferation, apoptosis, differentiation, and gene expression. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs derived from large transcripts. Mutations and disorders of lncRNAs are closely related to the development of osteoarthritis. Abnormal expression of lncRNAs in osteoarthritic cartilage regulates the synthesis and decomposition of the cartilaginous ECM. Therefore, the use of lncRNAs as nucleic acid drugs that regulate their targets may reduce ECM degradation, thereby delaying the pathological progression of osteoarthritis. In this review, the regulatory effects of lncRNAs on ECM in different cell behaviors related to OA are summarized. The roles of lncRNAs in the proliferation, apoptosis, differentiation, and ECM-related gene activity of chondrocytes, as well as the application of lncRNAs as potential gene therapy drugs for the repair and regeneration of osteoarthritic tissue, are also reviewed. A better understanding of the roles of lncRNAs in guiding chondrocyte behavior and ECM metabolism is critical for their future applications in osteoarthritis therapy and regenerative medicine.
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Estradiol decline can result in depressive disorders in females; nevertheless, the causes of this decline are unclear. In this study, we isolated estradiol-degrading Klebsiella aerogenes from the feces of premenopausal females with depression. In mice, gavaging with this strain led to estradiol decline and depression-like behaviors. The gene encoding the estradiol-degrading enzyme in K. aerogenes was identified as 3ß-hydroxysteroid dehydrogenase (3ß-HSD). Heterologously expressing 3ß-HSD resulted in Escherichia coli obtaining the ability to degrade estradiol. Gavaging mice with 3ß-HSD-expressing E. coli decreased their serum estradiol levels, causing depression-like behaviors. The prevalence of K. aerogene and 3ß-HSD was higher in premenopausal women with depression than in those without depression. These results suggest that the estradiol-degrading bacteria and 3ß-HSD enzymes are potential intervention targets for depression treatment in premenopausal women.
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Depresión , Enterobacter aerogenes , Estradiol , Microbiota , Premenopausia , Adulto , Animales , Femenino , Humanos , Ratones , 3-Hidroxiesteroide Deshidrogenasas/genética , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Depresión/metabolismo , Depresión/microbiología , Enterobacter aerogenes/genética , Enterobacter aerogenes/metabolismo , Escherichia coli/metabolismo , Heces/microbiología , Premenopausia/metabolismoRESUMEN
Background: Fibroblast growth factor 21 increased in population with type 2 diabetes mellitus (T2DM), while serum total testosterone often decreased in men with T2DM. This study aimed to investigate the relationship between the prevalence of coronary artery disease (CAD) and circulating FGF21 concentrations and serum testosterone in T2DM men. Methods: 490 men with T2DM from January 2021 to December 2021 were recruited from the Renmin Hospital of Wuhan University, and they were divided into CAD group (n=248) and control group (n=242). FGF21 were determined based on ELISA principle and serum total testosterone was measured in a liquid chromatography mass spectrometer LC/MS-8050 (Shimadzu, Japan). Logistic and restricted cubic spline analyses were performed to examine the association between the prevalence of CAD and circulating FGF21 concentrations and serum testosterone in T2DM men. The receiver operating curve (ROC) analysis was used to explore the predictive performance. Results: Circulating FGF21 levels were higher in T2DM men with CAD compared with those without CAD [214.63 (121.82, 348.64) pg/ml vs 166.55 (94.81,254.48) pg/ml, p<0.001], while serum total testosterone was lower [3.08 ± 0.07 ng/ml vs 3.76 ± 0.09 ng/ml, p<0.001]. The fully adjusted odds ratio (OR) and 95% confidence intervals (95%CI) was 2.956(1.409,6.201) for those in quartile 4 of FGF21 versus quartile 1 and the fully adjusted OR (95%CI) was 0.346(0.174,0.686) for those in quartile 4 of testosterone versus quartile 1. The receiver operating curve (ROC) analysis showed that the area under the curve (AUC) of combination of FGF21 and testosterone for predicting the occurrence of CAD in men with T2DM was 0.702 (95% CI: 0.667-0.741). Conclusion: Circulating FGF21 levels were positively associated with CAD in men with T2DM, whereas serum total testosterone levels showed an inverse correlation with CAD in diabetic men.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Factores de Crecimiento de Fibroblastos , Testosterona , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Masculino , Testosterona/sangreRESUMEN
OBJECTIVE: To investigate the antibacterial and anti-biofilm effects of colloidal bismuth subcitrate (CBS) on Porphyromonas gingivalis (P. gingivalis) in its planktonic and biofilm forms and also compare it with that of 0.2% chlorhexidine (CHX). DESIGN: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CBS were determined by the microdilution method; the bacteriostatic rate of CBS was determined by the MTT assay; the effect of CBS on the membrane integrity of P. gingivalis was investigated by the flow cytometric methods. The effects of CBS on the biomass and bacterial activity of biofilm were investigated. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) were used to investigate the activity and structure of biofilms. RESULTS: The MIC and MBC values were 18.75 µg/mL and 37.5 µg/mL. CBS could damage the cell membrane of P. gingivalis. CBS effectively inhibited biofilm formation and promoted dissociation at higher concentrations of 37.5 µg/mL and 75 µg/mL, respectively. The results also indicated an altered biofilm structure and reduced biofilm thickness and bacterial aggregation. CONCLUSIONS: CBS affected the metabolic and physiological processes of P. gingivalis, inhibited the formation of biofilm, and disrupted the mature biofilm.
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Biopelículas , Porphyromonas gingivalis , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Compuestos OrganometálicosRESUMEN
Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
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Caries Dental , Niño , Preescolar , Consenso , Caries Dental/prevención & control , Susceptibilidad a Caries Dentarias , Humanos , Salud BucalRESUMEN
AIM: Previous studies have provided evidence linking the DPEP1 gene to the risk of osteoarthritis (OA) in Europeans. In this study, we aimed to examine the relationship between DPEP1 gene and the susceptibility and clinical severity of OA in a Chinese Han population. METHODS: This study comprised two independent samples. For the discovery stage, 1022 patients with knee OA and 1864 controls were recruited. Fourteen tag single nucleotide polymorphisms (SNPs) covering the DPEP1 gene were selected and genotyped. Associated SNPs in the discovery data set were subsequently genotyped in the replication data set consisting of 826 hip OA cases and 1662 controls. Both genotypic and allelic genetic associations were tested. The relationship of significant SNPs to the expression of DPEP1 and its neighboring genes was examined using the GTEx database. RESULTS: A nonsynonymous SNP, rs1126464, was determined to be associated with the disease status of OA in both the discovery and replication stages (odds ratio [OR] 0.75, 95% confidence interval [95% CI] 0.68-0.82, P = 7.16 × 10-11 ). This SNP was further characterized as being significantly related to a higher Kellgren-Lawrence grade in OA patients (OR 0.64, 95% CI 0.55-0.74, P = 2.53 × 10-9 ). According to the GTEx data, SNP rs1126464 was significantly related to the gene expression of 15 genes in multiple types of human tissues. CONCLUSION: We reported a common DNA variant in the DPEP1 gene that contributes to the risk of OA, providing additional evidence that the DPEP1 gene plays a significant role in the pathological mechanisms of OA.
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Dipeptidasas/genética , Osteoartritis/genética , Polimorfismo de Nucleótido Simple , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Bases de Datos Genéticas , Femenino , Proteínas Ligadas a GPI/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/diagnóstico , Osteoartritis/etnología , Fenotipo , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tea tree essential oil (TTO) is extracted from the leaves of Melaleuca alternifolia by steam distillation. It is well known for its traditional medicinal uses, particularly for the treatment of bruises, insect bites, skin infections, vertigo, convulsions, toothache, and rheumatism. Earlier research has shown that TTO can effectively inhibit oral microorganisms in the root canals. Enterococcus faecalis (E. faecalis) has been considered to be associated with persistent root canal infections and root canal treatment failure. The biofilm of E. faecalis makes it more vigorous, toxic, and resistant to antibiotics. AIM OF THE STUDY: In this study, our aim was to evaluate the antimicrobial effects of TTO on planktonic E. faecalis and biofilms compared with 0.2% CHX. MATERIALS AND METHODS: We explored the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the bacteriostatic rate by MTT assay, the antimicrobial time by time-kill assay, and the effects on cell integrity, the biomass, and bacterial activity of E. faecalis biofilms. Finally, we investigated the microstructure changes of E. faecalis biofilms using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). RESULTS: The MIC and MBC values were 0.25% and 0.5%, the bacterial inhibition rate, time-kill was dosage dependent, and TTO can effectively destroy membrane integrity. SEM CLSM images revealed that TTO could reduce bacterial aggregation, biofilm thickness and inhibited biofilm formation. The effect of TTO was the same as that of 0.2% CHX at some specific concentrations. In summary, TTO has the potential to be effective against E. faecalis infections. CONCLUSIONS: TTO was able to inhibit E. faecalis by destroying cell membrane, inhibiting the formation of E. faecalis biofilms, and eliminating mature formed biofilms. In this study, TTO has the potential to be further developed as a novel antibacterial drug.
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Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Enterococcus faecalis/efectos de los fármacos , Aceite de Árbol de Té/farmacología , Biopelículas/crecimiento & desarrollo , Enterococcus faecalis/fisiología , Pruebas de Sensibilidad Microbiana , Hojas de la Planta/químicaRESUMEN
Nitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp tissues under both physiological and pathological conditions. However, little is known about the NO functions in dental pulp stem cells (DPSCs). We examined the direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the odontogenic capacity of rat DPSCs (rDPSCs). In the presence of NOC-18, rDPSCs were transformed into odontoblast-like cells with long cytoplasmic processes and a polarized nucleus. NOC-18 treatment increased alkaline phosphatase activity and enhanced dentin-like mineralized tissue formation and the expression levels of several odontoblast-specific genes, such as runt related factor 2, dentin matrix protein 1 and dentin sialophosphoprotein, in rDPSCs. In contrast, carboxy-PTIO, a NO scavenger, completely suppressed the odontogenic capacity of rDPSCs. This NO-promoted odontogenic differentiation was activated by tumor necrosis factor-NF-κB axis in rDPSCs. Further in vivo study demonstrated that NOC-18-application in a tooth cavity accelerated tertiary dentin formation, which was associated with early nitrotyrosine expression in the dental pulp tissues beneath the cavity. Taken together, the present findings indicate that exogenous NO directly induces the odontogenic capacity of rDPSCs, suggesting that NO donors might offer a novel host DPSC-targeting alternative to current pulp capping agents in endodontics.
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Pulpa Dental/citología , Donantes de Óxido Nítrico/farmacología , Compuestos Nitrosos/farmacología , Odontogénesis/efectos de los fármacos , Células Madre/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Pulpa Dental/efectos de los fármacos , Masculino , Odontoblastos/citología , Odontoblastos/efectos de los fármacos , Ratas Wistar , Células Madre/citologíaRESUMEN
OBJECTIVES: To evaluate the wound healing process following direct pulp capping with demineralized bone matrix (DBM) and calcium hydroxide (Ca(OH)2). METHODS: Fifty 8-weeks-old SPF Wistar male rats were divided into two groups: one was the DBM treated group, and the other was the Ca(OH)2 treated group. Pulpotomy was performed on the maxillary first molar of one side of each rat, and the another side was left as the blank control. Rats were sacrificed after each observation period (1, 3, 7, 14 and 28 days) and specimen slices were made. Hematoxylin-Eosin (HE) staining was used for observing the changes of pulp tissue, and immunohistochemical staining was used for observing the expression of reparative dentinogenesis-related factors runt transcription factor 2 (Runx2), type I collagen (COL I), osteocalcin (OCN) and dentin sialoprotein (DSP). RESULTS: Inflammatory cell infiltration (ICI) and pulp tissue disorganization (PTD) could be observed in both the DBM and Ca(OH)2 groups at all observation periods. The DBM group showed slighter ICI on 1 and 28 days and milder PTD on 28 days, with a significant difference (P<0.05). Reparative dentin formation (RDF) could initially be observed on 14 days postoperatively, and the DBM group showed more regular and thinner RDF with significant differences on 14 and 28 days compared with the Ca(OH)2 group (P<0.05). In both groups, the expression of Runx2, COL I, DSP and OCN were positive. Generally, the expression of these four factors in the DBM group was stronger than the Ca(OH)2 group on the same observation periods. CONCLUSIONS: DBM had the ability of inducing odontoblast differentiation and promoting dentinogenesis. DBM could initiate physiologic wound healing in pulp and had the ability to promote reparative dentin formation. Consequently, DBM may be an acceptable alternative for direct pulp capping.