SSEA-4 positive dental pulp stem cells from deciduous teeth and their induction to neural precursor cells.

BACKGROUND: Stage-specific embryonic antigen-4 (SSEA-4) is a marker for the identification of multipotent embryonic cells. It is also positive in neuroepithelial cells, precursor neural cells (NPC), and human dental pulp cells. The aim of this study was to evaluate the potential morphodifferentiation and histodifferentiation to NPC of SSEA-4 positive stem cells from human exfoliated deciduous teeth (SHED). METHODS: A SHED population in culture, positive to SSEA-4, was obtained by magnetic cell separation. The cells were characterized by immunohistochemistry and flow cytometry. Subsequently, a neurosphere assay was performed in a medium supplemented with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF); afterward, cells were neurodifferenciated with a neurobasal medium. Finally, indirect immunohistochemistry was performed to identify neuronal markers. RESULTS: The morphological and histological changes in the SSEA-4 positive SHEDs were observed after induction with epidermal and fibroblast growth factors in neurobasal culture medium. At the end of induction, the markers Nestin, TuJ-1, and GFAP were identified. CONCLUSIONS: The findings show that SSEA-4 positive SHEDs have a behavior similar to neuronal precursor cells. Our findings indicate that the dental pulp of deciduous teeth is a promising source for regeneration therapies associated with neurodegenerative diseases or peripheral nerve alterations.

Qualitative validation of audiovisual educational material for use on rheumatoid arthritis patients.

Medication compliance is critical to achieve therapeutic efficacy in patients with rheumatoid arthritis; however, among other factors, low patient-health literacy plays a negative role. Therefore, the development and validation of audiovisual educational material with the participation of health specialists and patients could lead to an improved level of compliance with treatment, while favoring its acceptance. To design and validate audiovisual educational material generated by a multidisciplinary and participative group of patients and health specialists. This study was carried out using a sequential methodology, including qualitative and quantitative techniques: (1) a non-participative observational study with patients and a non-systematic literature search were performed to identify conceptual topics. (2) Pilot videos were qualitatively assessed by patients and health specialists (focus groups and expert committees). (3) Improved versions of seven videos were quantitatively evaluated by patients and specialists following qualitative criteria of attraction, understanding, involvement, acceptance and induction of action. 74 patients with RA, 10 rheumatologists, 4 pharmacists and 2 medical anthropologists participated in the different phases of validation. A total of seven videos lasting 3 min each were generated, incorporating the most relevant suggestions by patients and healthcare professionals. The final version of the videos led to a mean compliance of 96.04 ± 5.2%, according to a representative group of patients and a mean 89.6 ± 9.4%, according to health professionals. With the participation of both patients and health specialists, seven audiovisual educational video recordings were developed and validated, reaching high levels of compliance in accordance with international criteria.

TGF-ß1 signaling inhibit the in vitro apoptotic, infection and stimulatory cell response induced by influenza H1N1 virus infection on A549 cells.

Influenza A virus (IAV) infection induces host cell responses that could derive in inflammatory and apoptotic response. In this respect, in multiple pathological situations, TGF-ß1 has shown anti-inflammatory effect, but its role during IAV infection is poorly understood. Interestingly, recent profiling expression studies have suggested that the TGF-ß1 pathway could be functionally related to the IAV infection's host response. To gain an understanding of the involvement of TGF-ß1's signaling pathway during IAV infection, we compared different apoptotic proteins such as TNFR1, Fas ligand, XIAP, cIAP, among others proteins, and pro-inflammatory elements like IL-1ß in the A549 cells during IAV infection (H1N1/NC/99), with and without 1 h of pre-treatment with TGF-ß1. Pre-incubation with TGF-ß1 significantly inhibited apoptosis and the presence of pro-apoptotic factors. Moreover, the relative abundance of immunodetected IAV M1 protein along 24 -h post-infection period was abridged, which correlated with a disminished infectious viral progeny Additionally, caspase 1 activation and increase of IL-1ß induced by IAV infection was also reduced by TGF-ß1 signaling activation. Whereas IAV infection increase of Smad-7 and, as consequence, partially inhibiting Smad2/3 phosphorylation, pre-treatment with TGF-ß1 blocked IAV-dependent Smad7 induction and prevented Smad2/3 signaling shutdown. All these data suggest the role of TGF-ß1 signaling pathway in the control of host cell response induced by the IAV infection and identify a potential clinical target to modulate acute cell death.

Corrigendum to "Subchronic Infection of Porphyromonas gingivalis and Tannerella forsythia Stimulates an Immune Response but Not Arthritis in Experimental Murine Model".

[This corrects the article DOI: 10.1155/2017/2052938.].

Subchronic Infection of Porphyromonas gingivalis and Tannerella forsythia Stimulates an Immune Response but Not Arthritis in Experimental Murine Model.

Studies have proposed that Porphyromonas gingivalis (Pg) and Tannerella forsythia (Tf) promote a nonspecific inflammatory response that could produce systemic disease. Oral inoculation of Pg and Tf on the immune and arthritis response was evaluated in BALB/C mice divided into four groups: (1) sham; (2) food contaminated with Pg/Tf; (3) complete Freund's adjuvant (CFA) + Pg/Tf; and (4) CFA alone. CFA was administered subcutaneously on days 1 and 14. The arthritis response was monitored for 21 days after day 14 of CFA administration. IL-1ß and IL-6 were determined in serum. T cell activation was evaluated by CD25 in salivary lymph nodes or mouse spleen. Pad inflammation appeared by day 19 in the CFA group, but animals with bacteria inoculation presented a delay. A significant increase in IL-6 was found in Groups 3 and 4, but not with respect to IL-1ß. We observed an increase in CD25 in cells derived from cervical nodes and in animals with bacteria inoculation and CFA. A local immune response was observed in mice inoculated with Pg and Tf (T cell activation); a systemic response was observed with CFA. Since pad inflammation was delayed by bacterial inoculation this suggests that local T cell activation could decrease pad inflammation.

Salivary ammonia levels and Tannerella forsythia are associated with rheumatoid arthritis: A cross sectional study.

The aim of this paper is to evaluate the relationship of salivary ammonium levels and the presence of bacteria with rheumatoid arthritis (RA) clinical disease activity in a cross-sectional study of Mexican patients. From a periodontal and disease activity standpoint, 132 consecutive RA patients fulfilling clinical criteria were evaluated. Ammonia levels (including peptidyl arginine deiminase activity) were evaluated by colorimetric assay and the presence of Porphyromonas gingivalis, Tannerella forsythia, and Prevotella intermedia was evaluated by polymerase chain reaction (PCR) technique. After a multivariate analysis, adjusting for clinical and serological parameters, a significant association was only observed between severe periodontitis and probing depth with high RA disease activity. Additionally, in contrast to P. gingivalis, the presence of T. forsythia was significantly associated with high disease RA activity even after multivariable adjustment analysis. There was also a significant increase in ammonium levels in the high RA activity group and a significant correlation between salivary ammonia and RA disease activity but not with autoantibody titers. Similarly, we observed a significant increase in the ammonium levels derived from the cultures of P. gingivalis and T. forsythia, with respect to P. intermedia and S. gordonii cultures, or even healthy donors. These results suggest that RA activity is associated with severe periodontitis, high salivary ammonium levels and the presence of T. forsythia.

Peripheral blood leptin and resistin levels as clinical activity biomarkers in mexican rheumatoid arthritis patients / Niveles en sangre periférica de leptina y resistina como biomarcadores de la actividad clínica de pacientes mexicanos con Artritis reumatoide

Objective. To evaluate the association between the clinical activity of RA patients and serum adipocytokines (Leptin, Adiponectin and Resistin) and inflammatory cytokines. Methods. All RA patients fulfilled ACR 1987 criteria and were treated with DMARDs. Adipocytokine and inflammatory cytokine levels were evaluated using ELISA. Results. 121 patients were included in the study. Stratifying according to DAS28 (low, moderate and high activity), there were significant differences for Leptin, Resistin, IL-6 and IL-17, however, no differences were seen for Adiponectin, TNFα or IL-1β. Clinical activity positively correlated with Leptin, Resistin, IL-17 and IL-6 levels, but not with Adiponectin, TNFα or IL-1β. Adiponectin levels negatively correlated with TNFα and positively correlated with IL-1β. IL-1β positively correlated with IL-6 and negatively correlated with TNFα and IL-17. Conclusion. Circulating Leptin, Resistin, IL-6 and IL-17 levels positively correlate with RA clinical activity in a manner independent of the subject's BMI. Complex relationships between inflammatory cytokines were observed in RA patients suggesting that other metabolic or inflammatory factors could be involved (AU)

Objetivo. Evaluar la asociación entre la actividad clínica de pacientes con Artritis reumatoide y adipocitocinas séricas (Leptina, Adiponectina y Resistina), citocinas inflamatorias (TNFα, IL-1β, IL-6, IFNγ e IL-17A). Métodos. Se seleccionaron pacientes con AR (ACR 1987) tratados con FARMEs. Los niveles de adipocitocinas y citocinas inflamatorias fueron evaluados por ELISA. Resultados. 121 pacientes se incluyeron en el estudio. La actividad clínica correlacionó positivamente con Leptina, Resistina, IL-6 e IL-17 pero no para Adiponectina, TNFα o IL-1β. Los niveles de Adiponectina se asociaron negativamente con TNFα y positivamente con IL-1β. Por su parte, IL-1β se asoció de manera positiva con IL-6 y negativamente con TNFα e IL-17. Conclusión. Los niveles circulantes de Leptina, Resistina, IL-6 e IL-17 se asociaron de manera positiva con la actividad clínica de pacientes con AR, independientemente del índice de masa corporal (IMC). Asimismo, en los pacientes con AR se observaron asociaciones complejas entre las adipocitocinas y citocinas, sugiriendo que otros factores tanto metabólicos como inflamatorios pudieran estar involucrados (AU)

Posible papel de Porphyromonas gingivalis en el desarrollo de la artritis reumatoide / Possible role of Porphyromonas gingivalis in the develpment of rheumatoid arthritis

Varios estudios han sugerido una asociación entre la periodontitissevera, la prevalencia de la bacteria Porphyromonas gingivalis y el desarrollo de artritis reumatoide. Como fundamento de esta relación, se ha observado que esta bacteria secreta una enzima, peptidil-arginina deiminasa, que es capaz de citrulinar proteínas del hospedero y así favorecer una respuesta autoinmune. Sin embargo, debido a la heterogeneidad de diseños experimentales, selección de pacientes y valoración de los desenlaces, los resultados no han mostrado la reproducibilidad deseada. Asimismo, observaciones recientes apuntan a que la actividad enzimática podría ser generada por otras especies bacterianas, lo que hace más compleja su relación. Sin embargo, por otro lado, algunos estudios sugieren que el tratamiento periodontal puede limitar el desarrollo de la artritis reumatoide.

Various studies have suggested a link between severe periodontitis,the prevalence of Porphyromonas gingivalis, and the development ofrheumatoid arthritis. As evidence of this relationship, P. gingivalis hasbeen found to secrete an enzyme, peptidyl arginine deiminase, which isable to citrullinate host proteins and thus help activate an autoimmuneresponse. However, due to the heterogeneity of experimental designs,patient selection, and assessment of clinical outcomes, the results havenot shown the desired reproducibility. Furthermore, recent fi ndingsindicate that the enzymatic activity may be produced by other species ofbacteria, which suggests the relationship is more complex. However, anumber of studies have shown that periodontal treatment could inhibitthe development of rheumatoid arthritis.

Peripheral blood leptin and resistin levels as clinical activity biomarkers in Mexican Rheumatoid Arthritis patients.

OBJECTIVE: To evaluate the association between the clinical activity of RA patients and serum adipocytokines (Leptin, Adiponectin and Resistin) and inflammatory cytokines. METHODS: All RA patients fulfilled ACR 1987 criteria and were treated with DMARDs. Adipocytokine and inflammatory cytokine levels were evaluated using ELISA. RESULTS: 121 patients were included in the study. Stratifying according to DAS28 (low, moderate and high activity), there were significant differences for Leptin, Resistin, IL-6 and IL-17, however, no differences were seen for Adiponectin, TNFα or IL-1ß. Clinical activity positively correlated with Leptin, Resistin, IL-17 and IL-6 levels, but not with Adiponectin, TNFα or IL-1ß. Adiponectin levels negatively correlated with TNFα and positively correlated with IL-1ß. IL-1ß positively correlated with IL-6 and negatively correlated with TNFα and IL-17. CONCLUSION: Circulating Leptin, Resistin, IL-6 and IL-17 levels positively correlate with RA clinical activity in a manner independent of the subject's BMI. Complex relationships between inflammatory cytokines were observed in RA patients suggesting that other metabolic or inflammatory factors could be involved.

A Prospective Follow-Up of Adipocytokines in Cohort Patients With Gout: Association With Metabolic Syndrome But Not With Clinical Inflammatory Findings: Strobe-Compliant Article.

The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up.Forty-one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann-Whitney U test, Fisher test, x, ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression.In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 ± 28.6 vs. 12.2 ± 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 ± 3.0 vs. 1.9 ± 1.2 ng/mL, P = 0.142 and 40.5 ± 26.8 vs. 38.0 ± 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P ≤ 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0.5) with metabolic variables or joint swelling.This study suggests that in patients with gout, concentrations of Lep and AdipoQ are more in line with the metabolic state than with clinical disease activity.

Leptin and adiponectin as predictors of disease activity in rheumatoid arthritis.

OBJECTIVES: To assess whether baseline levels of leptin and adiponectin predict disease activity or response to treatment in patients with RA at 6 months, 1 and 2 years of follow-up. METHODS: A consecutive cohort of patients, classified according to the 2010 ACR/EULAR RA criteria, was evaluated at baseline, 6 months, 1 and 2 years. All were treated with steroids and/or DMARDs. None received biologics. Blood was taken at a baseline to determine plasma anti-CCP, leptin and adiponectin. The relationship between leptin, adiponectin, DAS28 and changes in DAS28 was assessed by multivariable linear and logistic regression from baseline to follow-up. RESULTS: 127 patients completed 6 months, 91 one year and 52 two years of follow-up. All were female, mean age 45 years (18-70), time since onset of disease 7.5 years (0-36). A U-shaped relationship between DAS28 and leptin baseline levels was seen. Adjusting for different factors, leptin levels at baseline predicted higher DAS28 at 6 months and, in patients who were not overweight or obese, predicted disease activity at 6 months, 1 and 2 years. In patients who were not overweight or obese, baseline leptin was able to predict response to treatment at 6 and 12 months. CONCLUSIONS: In the short term, baseline leptin levels predict disease activity in all RA patients and response to treatment in RA patients with normal weight.