RESUMO
Periodontitis is an oral-cavity inflammatory disease and is the principal cause associated with tooth loss. Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are important proteases involved in periodontal tissue destruction. The omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been demonstrated to possess immunoregulatory properties in periodontitis. The aim of the study was to investigate the effects of ω-3 PUFA on inflammation and on the expression of MMP-2 and -9 in a murine periodontitis model. Twenty-four male C57BL/6 mice were divided into control mice (Control), control mice treated with ω-3 PUFA (O3), mice with periodontitis (P), and mice with periodontitis treated with ω-3 PUFA (P + O3). ω-3 PUFA were administered orally once a day for 70 days. Periodontitis in mice was induced by Porphyromonas gingivalis-infected ligature placement around the second maxillary molar. The mice were sacrificed, and blood and maxillary samples were collected. Flow cytometry was used to quantify tumor necrosis factor-alpha (TNFα), interleukin (IL)-2, IL-4, IL-5, and interferon-gamma. Histologic analysis and immunohistochemistry for MMP-2 and -9 were performed. The data were statistically evaluated using analysis of variance (ANOVA) and the Tukey post hoc test. Histological analysis showed that ω-3 PUFA supplementation prevented inflammation and tissue destruction and revealed that bone destruction was more extensive in the P group than in the P + O3 group (p < 0.05). Also, it decreased the serum expressions of TNFα and IL-2 and the tissue expression of MMP-2 and -9 in the periodontitis-induced model (p < 0.05). ω-3 PUFA supplementation prevented alveolar bone loss and periodontal destruction, probably by decreasing the expression of MMP-2 and MMP-9 and its immunoregulatory properties.
Assuntos
Ácidos Graxos Ômega-3 , Periodontite , Camundongos , Masculino , Animais , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Ácidos Graxos Ômega-3/farmacologia , Modelos Animais de Doenças , Fator de Necrose Tumoral alfa , Camundongos Endogâmicos C57BL , Periodontite/tratamento farmacológico , Periodontite/prevenção & controle , Periodontite/metabolismo , Inflamação , Dieta , Porphyromonas gingivalisRESUMO
Introduction: Hypermutated high-affinity immunoglobulin A (IgA), neutralizes toxins and drives the diversification of bacteria communities to maintain intestinal homeostasis although the mechanism underlies the impact of moderate aerobic exercise (MAE) on the IgA-generation via T-dependent (TD) is not fully know. Therefore, the aim of this study was to determine the effect of long-time MAE on the production of IgA through the TD pathway in Peyer´s patches of the small intestine from aged mice. Methods: MAE protocol consisted of twenty 3-month-old (young) BALB/c mice running in an endless band at 0° inclination and a speed of 10 m/h for 5 days a week and resting 2 days on the weekend until reaching 6-month-old (adulthood, n=10) or 24-month-old (aging, n=10). Groups of young, adult, or elderly mice were included as sedentary controls (n=10/per group). At 6 or 24 months old, all were sacrificed, and small intestine samples were dissected to prepare intestinal lavages for IgA quantitation by ELISA and to obtain suspensions from Peyer´s patches (PP) and lamina propria (LP) cells for analysis of T, B, and plasma cell subpopulations by flow cytometry and mRNA analysis expression by RT-qPCR of molecular factors related to differentiation of B cells to IgA+ plasma cells, class switch recombination, and IgA-synthesis. Statistical analysis was computed with two-way ANOVA (factor A=age, factor B=group) and p<0.05 was considered for statistically significant differences. Results: Compared to age-matched sedentary control, in exercised elderly mice, parameters were either increased (IgA concentration, IL-21, IL-10 and RDH mRNA expression), decreased (α-chain mRNA, B cells, mIgA+ B cells, mIgM+ B cells and IL-4 mRNA) or unchanged (PP mIgA+ plasmablasts and LP cyt-IgA+ plasma cells). Regarding the exercised adult mice, they showed an up-modulation of IgA-concentration, mRNA expression IL-21, IL-10, and RDH and cells (PP B and T cells, mIgM+ plasmablasts and LP cyt-IgA+plasma cells). Conclusion: Our findings suggest that MAE restored the IgA production in adult mice via the TD cell pathway but does not in aged mice. Other studies are necessary to know in more detail the impact of long-time MAE on the TD pathway to produce IgA in aging.
Assuntos
Imunoglobulina A , Linfócitos T , Humanos , Camundongos , Animais , Adulto , Lactente , Imunoglobulina A/genética , Interleucina-10 , Intestinos , RNA MensageiroRESUMO
Background: Nowadays elderly live longer but with more diseases and geriatric syndromes which can deteriorate their quality of life (QoL). Peritoneal dialysis (PD) is a renal replacement therapy which seeks to prolong an improve QoL; however, this is uncertain in elderly. Therefore, comparing QoL before and after starting dialysis in this population may let us know if there is a benefit at this level. Objective: Identify the QoL that patients have before and after PD. Material and methods: Longitudinal, comparative, prospective cohort, before and after study. Elderly with End Stage Renal Disease in whom hospitalization for PD was indicated. QoL was measured the instrument KDQOL SF 1.3. before and after 2 months of PD. Statistical Analysis: T paired test was performed with the basal value of QoL and after. Risks with 95% confidence intervals and X2 were obtained between the basal characteristics and the dependent variable of QoL. Results: 21 patients. After 2 months the QoL had an increment in comparison to basal QoL, but with no statistical significance (63.47 [SD 16.63] Vs 56.83 [16.01], P= 0.22. In the 7th decade PD increased QoL by 13.01 points (P= 0.04). Conclusions: PD increases QoL in the 7th decade.
Introducción: en la actualidad, los adultos mayores (AM) viven más años, pero con más enfermedades y síndromes geriátricos, lo cual puede deteriorar su calidad de vida (CV). La diálisis peritoneal (DP) es una terapia de sustitución renal que se pretende mejorar la esperanza y la CV, aunque esto es incierto en los AM. Por lo tanto, comparar la CV antes y después de iniciar la DP en esta población permite saber si existe un beneficio a ese nivel. Objetivo: identificar la CV con la que cuentan los AM antes y después de DP. Material y métodos: cohorte prospectiva, comparativa, tipo antes y después en AM con enfermedad renal terminal quienes se hospitalizaron para iniciar DP. La CV de determinó con el instrumento KDQOL SF 1.3, antes y dos meses después de la DP. El análisis estadístico consistió en t pareada entre el puntaje de CV basal y después. Entre las características basales y la variable CV se obtuvieron riesgos con intervalos de confianza al 95%, así como Chi cuadrada. Se tomó como significativa una p bilateral de ≤ 0.05. Resultados: 21 pacientes. Luego de 2 meses iniciada la DP, el valor promedio de la CV mostró un incremento en comparación con la CV basal, aunque no logra significancia estadística (63.47 [DE: 16.63] frente a 56.83 [DE: 16.01], p = 0.22. En la séptima década de la vida, la DP produjo un incremento de 13.01 puntos en la CV (p = 0.04). Conclusiones: la DP mejora la CV en AM de la séptima década de la vida.
Assuntos
Falência Renal Crônica , Diálise Peritoneal , Humanos , Idoso , Qualidade de Vida , Estudos Prospectivos , Diálise Renal , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: Microbiota and tight junction proteins (TJPs) are components of the gut barrier, and are considered stress targets that have deleterious effects on intestinal homeostasis. OBJECTIVES: This study aimed to evaluate the effects of chronic immobilization stress on selected small intestine homeostasis parameters. MATERIAL AND METHODS: Female BALB/c mice were divided into a stress group that underwent short-term immobilization for 2 h per day for 4 consecutive days, and a non-stressed control group (n = 6 per group). Proximal and distal small intestine samples were excised to assess colony-forming units per gram (CFU/g) of total bifidobacteria in selective agar plates, luminal albumin was assessed using immune-enzymatic assay, pro-inflammatory cytokines were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and TJPs (pore-forming, claudin (Cld)-2; pore-sealing, Cld-4; ambiguous, Cld-7, -12 and -15) were assessed with RT-qPCR and western blotting. RESULTS: Compared with the control group, the stress group had lower body weight and energy intake. In the distal region, the stressed mice had lower bifidobacteria count and messenger ribonucleic acid (mRNA) expression of Cld-2, Cld-4 and Cld-12, though they had more albumin and higher interleukin (IL)-6 mRNA expression. Within the proximal region, the stressed mice had higher mRNA expression of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), IL-6, Cld-7, Cld-12, and Cld-15, along with lower levels of IL-10 and Cld-4. However, mRNA and protein expression of TJPs were discordant. CONCLUSIONS: These findings indicate divergent stress-induced outcomes in the small intestine, evidenced by the elicitation of a pro-inflammatory response and decreased anti-inflammatory response in the duodenum, and by increased albumin transudation and decreased bifidobacterial growth in the distal region.
Assuntos
Citocinas , Intestino Delgado , Feminino , Animais , Camundongos , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Intestino Delgado/metabolismo , Interleucina-6/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , RNA Mensageiro/genética , Albuminas/metabolismo , Albuminas/farmacologia , Mucosa IntestinalRESUMO
Aerobic training (AT) is indicated in type 2 diabetes mellitus (T2DM) to control hyperglycaemia and inflammation. AT improves bone microarchitecture and resistance to fracture. The intensity of AT and the mechanisms that lead to the improvement in bone quality are still unknown. Using a mouse model of T2DM, we evaluated the effects of two intensities of forced AT. We divided mice into: sedentary (SED), T2DM-SED, low runners (LOW), T2DM-LOW, high runners (HIGH) and T2DM-HIGH. The AT for low was 8 m/minute (m/min); 5° slope or high 18 m/min; 15° slope for 2 months. We measured metabolic parameters, the serum cytokines concentration, lipocalin-2 (LCN-2) and adiponectin; and the tibial concentrations of LCN-2, tumour necrosis factor alpha (TNF-α) and protein carbonylation (CO). We evaluated femur morphometry and biomechanical properties. We performed multiple correlation analysis. The T2DM-LOW versus T2DM-SED group, shown an increase of interleukin (IL)-10 (417 ± 90 vs 102 ± 25 pg/mL) and improved trabecular bone (BV/TV: 31.8 ± 2.3 vs 19.25 ± 1.4%; Tb.Sp.: 1.62 ± 0.02 vs 2.0 ± 0.07 mm), by a decrease bone CO (3.4 ± 0.1 vs 6.0 ± 0.5 nmol/mg), bone TNF-α (84 ± 4 vs 239 ± 13 pg/mL) and LCN-2 (2887 ± 23 vs 3418 ± 105 pg/mL). The T2DM-HIGH versus T2DM-SED group showed a greater hypoglycaemic effect (228 ± 10 vs 408 ± 5 mg/dL), with improved cortical bone density (0.26 ± 0.012 vs 0.21 ± 0.007 mm) and fracture resistance (102 ± 8 vs 78 ± 5 MPa), by a reduction of bone TNF-α (77 ± 34 vs 239 ± 13 pg/mL); LCN-2 (2768 ± 20 vs 3418 ± 105 pg/mL) and CO (4.8 ± 0.5 vs 6.0 ± 0.5 nmol/mg). In conclusion, AT improves bone morphometry and biomechanical properties by reducing the bone inflammatory microenvironment.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Fator de Necrose Tumoral alfa , Osso e OssosRESUMO
Exercise encourages active and healthy aging, maintaining functional and physical capabilities. This study aimed to assess the effects of a long-term moderate aerobic exercise protocol on bone microarchitecture and fragility associated with chronic inflammation and oxidative stress in aging. Male BALB/c mice (n = 10 per group) underwent a moderate exercise protocol from 13 weeks to 27 (adulthood age) or 108 weeks of age (elderly age) and were then sacrificed. Age-match sedentary mice were included as a control group. Serum cortisol concentrations were determined by chemiluminescent immunoassay, C-reactive protein (CRP) by a turbidimetric assay, advanced glycation end-products (AGEs) and malondialdehyde (MDA) by fluorescent spectroscopy, and total glutathione (GSH) by colorimetric method. The right femur was dissected formorphometric and densitometricanalysis bycomputerized microtomography (µCT),and biomechanical properties were assessed usinga three-point bending device. Musclefrom the same extremitywas obtained to determine relative mRNA expression ofpro-inflammatory cytokines (TNF-α and IL-6) by RT-qPCR.Statistical differences were evaluated by two-way ANOVA and Holm-Sidak method post hoc with P < 0.05. In elderly mice, moderate exercise increased glutathione levels and microarchitecture complexity but decreased bone fragility and oxidative stress markers, cortisol, and pro-inflammatory cytokines. In conclusion, these results suggest a strong link between a pro-inflammatory state and age-conditioned oxidative stress on bone quality. Thus, on a human scale, moderate aerobic exercise may improve bone quality during aging.
Assuntos
Hidrocortisona , Estresse Oxidativo , Animais , Citocinas/metabolismo , Glutationa/metabolismo , Glutationa/farmacologia , Hidrocortisona/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Patients with type 2 diabetes mellitus (DM2) experience an increased risk of fractures and a variety of bone pathologies, such as osteoporosis. The suggested mechanisms of increased fracture risk in DM2 include chronic hyperglycaemia, which provokes oxidative stress, alters bone matrix, and decreases the quality of hydroxyapatite crystals. Docosahexaenoic acid (DHA), an omega-3 fatty acid, can increase bone formation, reduce bone loss, and it possesses antioxidant/anti-inflammatory properties. The present study aimed to determine the effect of DHA on altered osteoblast mineralisation and increased reactive oxygen species (ROS) induced by high glucose concentrations. A human osteoblast cell line was treated with 5.5 mM glucose (NG) or 24 mM glucose (HG), alone or in combination with 10 or 20 µM DHA. The collagen type 1 (Col1) scaffold, the expression of osteocalcin (OCN) and bone sialoprotein type-II (BSP-II), the alkaline phosphatase (ALP) specific activity, the mineral quality, the production of ROS and the mRNA expression of nuclear factor erythroid 2-related factor-2 (NRF2) were analysed. Osteoblasts cultured in HG and treated with either DHA concentration displayed an improved distribution of the Col1 scaffold, increased OCN and BSP-II expression, increased NRF2 mRNA, decreased ALP activity, carbonate substitution and reduced ROS production compared with osteoblasts cultured in HG alone. DHA counteracts the adverse effects of HG on bone mineral matrix quality and reduces oxidative stress, possibly by increasing the expression of NRF2.
RESUMO
La curcumina es una sustancia derivada de una planta llamada Curcuma longa. A esta sustancia se le han atribuido diversos efectos terapéuticos. En relación con la clínica dental, se ha observado que, además de ayudaren el control del dolor, ha sido efectiva contra la periodontitis, estomatitis y mucositis pediátrica. El control del dolor e inflamación son aspectos muy importantes para la mayoría de los tratamientos en odontología; la búsqueda de nuevas alternativas analgésicas y antiinflamatorias que, en comparación con las actuales, sean más eficientes, efectivas y tengan menos efectos colaterales es uno de los grandes retos de las ciencias biomédicas. La presente revisión muestra algunas evidencias científicas de los efectos de la curcumina como un antiinflamatorio y analgésico, con el propósito de sentar las bases para futuros estudios clínicos y de ciencia básica que aporten un mayor entendimiento de los procesos celulares, bioquímicos, moleculares, fisiológicos y farmacológicos de la curcumina como una sustancia potencialmente útilen el consultorio dental.
Curcumin is a substance derived from the plant Curcuma longa andone that has been attributed a range of therapeutic eff ects. In dentalpractice, curcumin has not only been found to help with pain control, buthas also been eff ective against periodontitis, stomatitis, and pediatricmucositis. Controlling pain and infl ammation are both very importantaspects of most dental treatments. The search for more effi cient andeff ective analgesic and anti-infl ammatory alternatives with fewerside eff ects compared to those currently used is one of the greatestchallenges for biomedical science. This review presents some of thescientifi c evidence of the eff ects of curcumin, both as an analgesic andan anti-infl ammatory agent, in order to establish the foundations forfurther clinical and basic science studies that will provide a greaterunderstanding of the cellular, biochemical, molecular, physiological,and pharmacological processes of curcumin as a potentially usefulsubstance in dental practice.
Assuntos
Humanos , Analgésicos/classificação , Anti-Inflamatórios não Esteroides/classificação , Curcumina/farmacologia , Curcumina/uso terapêutico , Antineoplásicos/classificação , Antineoplásicos/uso terapêutico , Antissépticos Bucais/classificação , Antissépticos Bucais/uso terapêutico , Doenças Periodontais/tratamento farmacológico , Estomatite/tratamento farmacológicoRESUMO
The Cry1Ac toxin from Bacillus thuringiensis is used commercially as a bio-insecticide and is expressed in transgenic plants that are used for human and animal consumption. Although it was originally considered innocuous for mammals, the Cry1Ac toxin is not inert and has the ability to induce mucosal and systemic immunogenicity. Herein, we examined whether the Cry1Ac toxin promotes macrophage activation and explored the signalling pathways that may mediate this effect. Treatment of primary and RAW264.7 macrophages with the Cry1Ac toxin resulted in upregulation of the costimulatory molecules CD80, CD86 and ICOS-L and enhanced production of nitric oxide, the chemokine MCP-1 and the proinflammatory cytokines TNF-α and IL-6. Remarkably, the Cry1Ac toxin induced phosphorylation of the mitogen-activated protein kinases (MAPKs) ERK1/2, JNK and p38 and promoted nuclear translocation of nuclear factor-kappa B (NF-κB) p50 and p65. p38 and ERK1/2 MAPKs were involved in this effect, as indicated by the Cry1Ac-induced upregulation of CD80 and IL-6 and TNF-α abrogation by the p38 MAPK inhibitor SB203580. Furthermore, treatment the MEK1/2 kinase inhibitor PD98059 blocked increases in MCP-1 secretion and augmented Cry1Ac-induced ICOS-L upregulation. These data demonstrate the capacity of the Cry1Ac toxin to induce macrophage activation via the MAPK and NF-κB pathways.
Assuntos
Proteínas de Bactérias/toxicidade , Endotoxinas/toxicidade , Proteínas Hemolisinas/toxicidade , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Toxinas de Bacillus thuringiensis , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Quimiocina CCL2/biossíntese , Feminino , Interleucina-6/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Subunidade p50 de NF-kappa B/metabolismo , Nitritos/metabolismo , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Células RAW 264.7 , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
Abstract: cranial sutures are specialized structures composed of the sutural mesenchyme, the overlying scalp, the dura and osteogenic fronts. Each one of these structures express important proteins for osteogenic maturation, membranous ossification of skull bones, and homeostasis of cranial sutures in a differential, spatial and temporal manner. These proteins include fibroblast growth factor (FGF) and its receptors (FGFR), the transforming growth factor beta (TGF-beta), bone morphogenetic proteins (BMPs), as well as transcription factors TWIST and MSX2, among others. The alteration in the expression of one or more of these proteins causes multiple pathological conditions; one of them is the premature closure of one or more cranial sutures, known as craniosynostosis. This malformation is commonly treated with surgery. However, advances in the fields of molecular and cellular biology have allowed to conduct research on some proteins involved in the development of craniosynostosis. The results of these studies can lead to future preventive therapeutic strategies that may be used as a complement to the surgical treatment of craniosynostosis. Possible strategies include the use of specific drugs that can regulate the expression and activation of FGF signaling pathways, TGF-beta or BMPs, to prevent or avoid craniosynostosis or re-synostosis after a surgery.
Resumen: las suturas craneales son estructuras especializadas compuestas por el mesénquima sutural, el pericráneo suprayacente, la duramadre y los frentes osteogénicos. Cada una de estas estructuras expresan de forma diferencial, espacial y temporalmente, proteínas importantes para la maduración osteogénica, la osificación membranosa de los huesos calvarios y la homeostasis de las suturas craneales. Estas proteínas incluyen el factor de crecimiento fibroblástico (FGF) y sus receptores (FGFR), el factor de crecimiento transformante beta (TGF-beta), las proteínas morfogenéticas óseas (BMPs), así como factores de transcripción TWIST y MSX2, entre otros. La alteración en la expresión de una o varias de estas proteínas provoca múltiples condiciones patológicas, una de ellas es el cierre prematuro de una o varias suturas craneales, conocido como craneosinostosis. Esta malformación es comúnmente tratada con cirugía. Sin embargo, los avances en los campos de la biología molecular y celular han permitido investigar algunas proteínas que participan en el desarrollo de la craneosinostosis. Los resultados de estos estudios pueden generar futuras estrategias terapéuticas preventivas o que complementen los tratamientos quirúrgicos de la craneosinostosis. Algunas estrategias posibles son el uso de fármacos específicos que puedan regular la expresión y activación de las vías de señalización del FGF, el TGFbeta o de las BMPs, para prevenir la craneosinostosis o evitar la resinostosis tras una cirugía.