The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.

Detection of skin wrinkles and quantification of roughness using a novel image processing technique from a dermatoscope device.

OBJECTIVE: Cutaneous relief analysis is crucial in the development of new skincare products, as well as in the evaluation of dermatological treatments. The analysis can be performed by qualitative or quantitative methods. We propose a new algorithm to detect wrinkles and quantify skin roughness by image processing from a dermatoscope. METHODS: A clinical study was carried out with 33 research participants, and images were collected with the dermatoscope and PRIMOS equipment for wrinkle evaluation at two different times: Day 0 (D0) and 45 days (D45) after the use of a dermocosmetic product. Later, a new algorithm was developed to detect wrinkles in the acquired images by applying filters and image transformations that generate a segmented image highlighting the wrinkles. A roughness calculation method is proposed from the pixels belonging to wrinkles. RESULTS: Correlation between the values obtained by the PRIMOS equipment and the proposed system was verified. No correlation was found for data obtained at D0; however, there was correlation at time D45 by Spearman's similarity coefficient. By comparing roughness between times D0 and D45, the treatment was statistically significant for both PRIMOS and the proposed methodology data. CONCLUSION: The wrinkle detection algorithm, in addition to the roughness calculation, demonstrated a sensitivity comparable to the PRIMOS system in evaluating the effectiveness of the dermocosmetic treatment. SIGNIFICANCE: Considering the simplicity of the dermatoscope design compared to other established devices such as PRIMOS, the proposed system is promising as an alternative for dermatological evaluations.

The Nurr7 agonist Cytosporone B differentially regulates inflammatory responses in human polarized macrophages.

The orphan nuclear receptor Nur77 is involved in diverse cellular processes such as inflammation, proliferation, differentiation and survival. Stimuli like lipopolysaccharide (LPS) and tumor necrosis factor (TNF) increase Nur77 expression in human and murine macrophages, and it has been proposed that Nur77 plays a major role in dampening the inflammatory response. Here, we evaluated the expression and function of Nur77 in human anti-inflammatory and pro-inflammatory macrophages derived from blood monocytes cultured with macrophage colony-stimulating factor (M-MDMs) or granulocyte/macrophage colony-stimulating factor (GM-MDMs), respectively. Nur77 mRNA expression was significantly enhanced in M-MDMs compared with GM-MDMs, both constitutively and upon exposure to Toll-like receptor (TLR)2, 3, and 4 ligands. Nur77 activation with the agonist Cytosporone B (CsnB) significantly suppressed the production of TNF, interleukin (IL)-1ß, IL-6, and IL-8 in GM-MDMs stimulated with LPS. In contrast, it tended to enhance the production of the anti-inflammatory cytokine IL-10. This effect was associated with reduced NF-κB p65 nuclear translocation. Similarly, Nur77 knockdown enhanced TNF production in GM-MDMs. CsnB effectively stimulated the transactivation activity of Nur77 in M-MDMs, but it did not alter cytokine synthesis or p65 nuclear translocation. However, Nur77 seemed to have a role in maintaining the anti-inflammatory profile of M-MDMs, since Nur77-deficient M-MDMs constitutively produced higher levels of TNF transcripts. Thus, in the absence of exogenous agonists, Nur77 activity favors the anti-inflammatory function of M-MDMs, whereas agonistic activation of this receptor preferentially drives attenuation of inflammation in inflammatory macrophages.

Placental Nutrient Transporters and Maternal Fatty Acids in SGA, AGA, and LGA Newborns From Mothers With and Without Obesity.

Adverse environmental factors in early life result in fetal metabolic programming and increased risk of adult diseases. Birth weight is an indirect marker of the intrauterine environment, modulated by nutrient availability and placental transport capacity. However, studies of placental transporters in idiopathic birth weight alterations and in maternal obesity in relation to neonatal metabolic outcomes are scarce. We aimed to analyze the placental nutrient transporter protein expression in small (SGA, n = 14), adequate (AGA, n = 18), and large (LGA n = 10) gestational age term for newborns from healthy or obese mothers (LGA-OB, n = 9) and their association with maternal fatty acids, metabolic status, placental triglycerides, and neonatal outcomes. The transporter expression was determined by Western blot. The fatty acid profile was evaluated by gas chromatography, and placental triglycerides were quantified by an enzymatic colorimetric method. GLUT1 was higher in LGA and lower in SGA and positively correlated with maternal HbA1c and placental weight (PW). SNAT2 was lower in SGA, while SNAT4 was lower in LGA-OB. FATP1 was lower in SGA and higher in LGA. SNAT4 correlated negatively and FATP1 correlated positively with the PW and birth anthropometry (BA). Placental triglycerides were higher in LGA and LGA-OB and correlated with pregestational BMI, maternal insulin, and BA. Maternal docosahexaenoic acid (DHA) was higher in SGA, specifically in male placentas, correlating negatively with maternal triglycerides, PW, cord glucose, and abdominal perimeter. Palmitic acid (PA) correlated positively with FATP4 and cord insulin, linoleic acid correlated negatively with PA and maternal cholesterol, and arachidonic acid correlated inversely with maternal TG and directly with FATP4. Our study highlights the importance of placental programming in birth weight both in healthy and obese pregnancies.

Patterns of regulatory behavior in the still-face paradigm at 3 months: A comparison of Brazilian and Portuguese infants.

Three infant regulatory behavior patterns have been identified during the Face-to-Face Still-Face paradigm (FFSF) in prior research samples: a Social-Positive Oriented pattern (i.e., infants exhibit predominantly positive social engagement), a Distressed-Inconsolable pattern (i.e., infants display conspicuous negative affect that persists or increases across FFSF episodes), and a Self-Comfort Oriented pattern (e.g., infants primarily engage in self-comforting behaviors such as thumb-sucking). However, few studies have examined these patterns outside US and European countries or evaluated potential cross-country differences in these patterns. In this study, we compared the regulatory behavior patterns of 74 Brazilian and 124 Portuguese infants in the FFSF at 3 months of age, and evaluated their links to demographic and birth variables. The prevalence of the three regulatory patterns varied by country. The most frequent pattern in the Portuguese sample was the Social-Positive Oriented, followed by the Distressed-Inconsolable and the Self-Comfort Oriented. However, in the Brazilian sample, the Distressed-Inconsolable pattern was the most prevalent, followed by the Social-Positive Oriented and the Self-Comfort Oriented. Moreover, in the Brazilian sample, familial SES was higher among infants with a Social-Positive pattern whereas 1st-minute Apgar scores were lower among Portuguese infants with a Distressed-Inconsolable Oriented pattern of regulatory behavior. In each sample, Social Positive pattern of regulatory behavior was associated with maternal sensitivity, Self-Comfort Oriented pattern of regulatory behavior with maternal control, and Distressed-Inconsolable pattern with maternal unresponsivity.

Not everything is as it seems: a rare form of metastatic breast cancer.

Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among females worldwide. Despite all therapeutic advances, metastatic breast cancer is still associated with a median overall survival of 3 years. Alongside this condition, bladder metastases of solid neoplasms are rarely observed. In this setting, the secondary bladder tumors with an origin in breast cancer occur in 2.5% of cases in some series. The authors report the case of a 68-year-old female with stage IV breast cancer (bone metastasis) treated with anastrozole, who presented with peripheral edema and renal failure with a creatinine clearance of 12.5 mL/min. After hospital admission, the patient was diagnosed with new liver lesions and bladder involvement with bilateral hydronephrosis. She was submitted to bilateral percutaneous nephrostomies with improvement in renal function. There was a high suspicion of primary bladder tumor in this patient who was a previous smoker, with a family history of high-grade bladder carcinoma (her mother). Liver and transurethral biopsies were performed, and histological examination was consistent with breast cancer metastases. The patient started treatment with capecitabine and denosumab, remaining clinically stable after 3 months of treatment. This case report underlines the diagnostic challenges of bladder metastases in a patient with multiple risk factors for bladder cancer and without evident clinical symptoms. Even though this is a rare entity, the close surveillance of metastatic breast cancer is important in order to allow early detection of new metastatic sites and their treatment to preserve the quality of life in these patients.

Not everything is as it seems: a rare form of metastatic breast cancer

Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among females worldwide. Despite all therapeutic advances, metastatic breast cancer is still associated with a median overall survival of 3 years. Alongside this condition, bladder metastases of solid neoplasms are rarely observed. In this setting, the secondary bladder tumors with an origin in breast cancer occur in 2.5% of cases in some series. The authors report the case of a 68-year-old female with stage IV breast cancer (bone metastasis) treated with anastrozole, who presented with peripheral edema and renal failure with a creatinine clearance of 12.5 mL/min. After hospital admission, the patient was diagnosed with new liver lesions and bladder involvement with bilateral hydronephrosis. She was submitted to bilateral percutaneous nephrostomies with improvement in renal function. There was a high suspicion of primary bladder tumor in this patient who was a previous smoker, with a family history of high-grade bladder carcinoma (her mother). Liver and transurethral biopsies were performed, and histological examination was consistent with breast cancer metastases. The patient started treatment with capecitabine and denosumab, remaining clinically stable after 3 months of treatment. This case report underlines the diagnostic challenges of bladder metastases in a patient with multiple risk factors for bladder cancer and without evident clinical symptoms. Even though this is a rare entity, the close surveillance of metastatic breast cancer is important in order to allow early detection of new metastatic sites and their treatment to preserve the quality of life in these patients.

El reconocimiento como propuesta metodológica de calidad en el aprendizaje / The Recognition as a Quality Methodology Proposal in the Learning Process

En el terreno de la educación, la pregunta por la formación es permanente y controvertida. Adicionalmente, con los evidentes cambios en la producción, apropiación y transmisión del conocimiento global, continúa siendo pertinente cuestionar el papel de la educación en la transformación del sujeto, en la vía de la autonomía y la toma de decisiones frente a su proceso educativo y a su responsabilidad como persona comprometida con el conocimiento como factor de desarrollo social. En este contexto, se rescatan los resultados de una investigación realizada en 1995 sobre el reconocimiento como propuesta metodológica de calidad en el aprendizaje, por considerar que sus planteamientos mantienen vigencia frente a los actuales cambios en la estructura educativa.

In the education field, the question for the holistic formation is continuous and controversial. Moreover, with the obvious changes in the global knowledge production, apprehension and transmission, is crucial asking for the role of the education in the changes of the individual toward autonomy and take decisions in relationship with the educational process and the responsibility like a person sharing with knowledge like an issue of social development. In this context, this paper, presents results of an in- vestigation made on 1995, about the recognition value like a methodology proposal of learning quality, for consider their propositions to be in force into an educational structure.