Luz-Stella Rodríguez

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are systemic autoimmune diseases associated with increased cardiovascular risk and metabolic alterations. We applied ¹H NMR spectroscopy to profile lipoproteins and metabolites in women with RA, SLE, and healthy controls. Both RA and SLE showed shared alterations in HDL metabolism, including reduced HDL particle size and lower concentrations of small HDL particles compared with controls. RA exhibited additional changes, notably a significant reduction in small LDL particle concentration. Metabolite profiling further differentiated RA, revealing significantly lower circulating levels of glutamine, alanine, and GlycB. Correlation analyses demonstrated that in RA, LDL particle concentrations were positively associated with disease activity (DAS28-ESR), and large LDL particles correlated positively with IFN-γ and VEGF. In SLE, HDL particle measures were associated with complement components, with small HDL particles positively correlated with C3 and HDL particle size inversely correlated with C3, while large LDL particles correlated positively with IL-6 and negatively with MDC. Together, these results indicate that RA and SLE share common lipoprotein alterations, while RA displays additional metabolic changes. NMR-derived lipoprotein and metabolite profiles may provide complementary information for assessing inflammation and cardiovascular risk in autoimmune diseases.

Background: Understanding the mechanisms underlying dental pain caused by pulpitis in humans has led to the development of animal models, such as the rat, which enable the study of the mechanisms underlying inflammation; the use of these models is considered ethically justified when the anticipated scientific benefits outweigh the potential impacts on animals in the harm/benefit balance. Objective: To develop a rat model of mechanically induced pulpitis and to evaluate the potential impact on animal well-being. Methods: Pulpitis was mechanically induced in male Lewis rats (13–16 weeks, 350–400 g) which were anesthetized and endotracheally intubated. Following pulp exposure, the cavity was sealed with either amalgam (n = 10) or zinc phosphate cement (n = 10). Following recovery and return to their housing, behavioral assessments and histological evaluations using Hematoxylin and Eosin (H&E) staining were conducted in separate cohorts at two time points: 3 h and 5 days following the procedure. Results: A standardized model of mechanically induced pulpitis was established and verified clinically and by histopathological analysis, which showed evidence of the inflammatory process and revealed no statistically significant differences in the scoring of pain, discomfort, or distress, nor in the measurements of food and water consumption or body weight. Conclusions: The behavioral assessments conducted in this study supported the implementation of a safe and easily reproducible model for future research aimed at elucidating the mechanisms underlying pulp inflammation.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune diseases associated with chronic inflammation and cardiovascular risk. This study aimed to identify metabolic alterations in Colombian women with RA and SLE to discover potential biomarkers. Plasma samples were analyzed using LC-QTOF-MS and GC-QTOF-MS. Correlation network analysis assessed relationships between metabolites, cytokines, and HDL levels. A generalized linear model (GLM) combined metabolite scores, and ROC analysis evaluated their predictive performance. Significant metabolic changes were observed, including decreased phospholipids and sphingolipids, and increased glycerolipids in RA and SLE compared to healthy controls. The metabolite–cytokine network revealed correlations between FA 18:0 and DG 37:7 with cytokines, linking lipid metabolism to inflammation. PS O-40:3 and FA 18:0 in RA and PC O-28:0 and DG 37:7 in SLE distinguished patients from healthy controls. The combination of PS O-40:3 and FA 18:0 in RA (AUC = 0.997) and PC O-28:0 and DG 37:7 in SLE (AUC = 0.949) demonstrated high predictive performance. PE O-42:5 was positively correlated with HDL, suggesting a potential protective role against cardiovascular disease. These findings highlight lipid metabolism’s role in RA and SLE and support specific metabolites as biomarkers for disease differentiation, inflammation, and cardiovascular risk. These insights could lead to improved diagnostics and targeted treatments for these autoimmune diseases.

The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal–Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1β, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.

This study quantified the production of the pro-resolving agent Resolvin E1 by peripheral blood mononuclear cells (PBMC) from 20 systemically healthy volunteers with and without periodontitis after stimulation with lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg). Ten periodontitis patients and 10 healthy volunteers (30-50 years old), matched by age and sex, were recruited. Peripheral blood mononuclear cells were isolated and stimulated in culture plates for 24 hours with Pg LPS. Resolvin E1 levels were measured in the supernatants by enzyme-linked immunosorbent assay. Significantly higher production of Resolvin E1 was observed in both groups when stimulated with LPS compared to baseline levels (p<0.001). A significant increase in Resolvin E1 was observed in the presence of Lipopolysaccharide in the patients with periodontitis compared to the healthy group (p=0.0019). Resolvin E1 levels may reflect a measure of resolution of inflammation that warrants further clinical investigation.

The response of antibody-secreting cells (ASC) induced by dengue has only recently started to be characterized. We propose that young age and previous infections could be simple factors that affect this response. Here, we evaluated the primary and secondary responses of circulating ASC in infants (6–12 months old) and children (1–14 years old) infected with dengue showing different degrees of clinical severity. The ASC response was delayed and of lower magnitude in infants, compared with older children. In primary infection (PI), the total and envelope (E) protein-specific IgM ASC were dominant in infants but not in children, and a negative correlation was found between age and the number of IgM ASC (rho = −0.59, P = 0.03). However, infants with plasma dengue-specific IgG detectable in the acute phase developed an intense ASC response largely dominated by IgG and comparable to that of children with secondary infection (SI). IgM and IgG produced by ASC circulating in PI or SI were highly cross-reactive among the four serotypes. Dengue infection caused the disturbance of B cell subsets, particularly a decrease in the relative frequency of naïve B cells. Higher frequencies of total and E protein-specific IgM ASC in the infants and IgG in the children were associated with clinically severe forms of infection. Therefore, the ASC response induced by dengue is highly influenced by the age at which infection occurs and previous immune status, and its magnitude is a relevant element in the clinical outcome. These results are important in the search for correlates of protection and for determining the ideal age for vaccinating against dengue.

Background: due of capsaicin effect on the control of various inflammatory mediators, it has been proposed to modulate inflammatory processes caused by physical assaults to pulp tissue. Purpose: to evaluate the effect of capsaicin diluted in 0.05 % ethanol and its vehicle on PGE2 production, IL-8, IL-6, IL-1β, and IL-12p70 in Human Fibroblasts Pulp (FPH). Methods: concentrations of PGE2, IL-8, IL-6, IL-1β, and IL-12p70 were analyzed by ELISA or flow cytometry in supernatants of FPH at 6 and 8 hours, after being stimulated with capsaicin 5*10-5 M and 2,5*10-5 M and ethanol 0.05% vehicle of capsaicin and compared with unstimulated cells. Results: ethanol 0.05% as a diluent capsaicin, is responsible for the effect on the decrease in the expression of PGE2, IL-8 and IL-6 at the times and concentrations evaluated; and IL-12p-70 was the only cytokine that increased significantly in the presence of capsaicin 2,5*10-5 M at 8h, it is statistically greater than ethanol 0.05%. Capsaicin and ethanol had not significant effect on IL-1β. Conclusion: the effect of capsaicin on FPH, is associated with ethanol 0.05% used as diluent and varies depending on time and the mediator analyzed.

Introducción. La vitamina D3 actúa como modulador de algunas células del sistema inmunitario, incluidas las células dendríticas. Varios estudios han reportado su importancia en la generación in vitro de células dendríticas tolerogénicas, similares en cuanto a fenotipo y función a las células dendríticas dérmicas CD141 productoras de IL-10 e inductoras de linfocitos T reguladores CD4+.Objetivo. Se compararon el fenotipo y las citocinas producidas por las células dendríticas generadas en ausencia o en presencia de la vitamina D3, y maduradas con lipopolisacáridos, así como su habilidad de inducir linfocitos T reguladores a partir de linfocitos T CD4+ vírgenes alogénicos.Materiales y métodos. Se aislaron células mononucleares de sangre periférica para seleccionar monocitos CD14+ y diferenciarlos in vitro de las células dendríticas en presencia o en ausencia de vitamina D3, y madurarlas con lipopolisacáridos. Se analizaron el fenotipo y los niveles de las citocinas en los sobrenadantes de cultivo. Se hizo un cocultivo de las células dendríticas con linfocitos T CD4+ vírgenes alogénicos y se determinaron las frecuencias de LTreg (vírgenes activados).Resultados. Las células dendríticas no estimuladas generadas con la vitamina D3 conservaron el CD14. Al activarlas con lipopolisacáridos, expresaron bajos niveles de C83, CD83 y CD86, HLA-DR, cantidades elevadas de IL-1β, IL-8 e IL-10, y una tendencia a la disminución de IL-6, IL-12p70 y TGF-β1 con respecto a las que no habían sido tratadas con la vitamina. La frecuencia de los LTreg vírgenes fue similar, aunque se observó una tendencia de las células dendríticas inmaduras generadas con la vitamina a inducir LTreg activados.Conclusión. Las células dendríticas generadas con vitamina D3 y tratadas con lipopolisacáridos presentaron un fenotipo ‘semimaduro’, así como la capacidad de secretar citocinas antiinflamatorias y citocinas promotoras de la reacción inflamatoria. Además, no se aumentó su capacidad de promover la polarización de LTCD4+ vírgenes alogénicos hacia LTreg.