Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits.

Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1-/- ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking ß1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating ß1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+ dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+ regulatory T cells (Tregs), and increased number of CD8+ T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+ T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.

Assessment of acute toxicity, genotoxicity, and anti-inflammatory activity of SteLL, a lectin from Schinus terebinthifolia Raddi. Leaves, in mice.

ETHNOPHARMACOLOGY RELEVANCE: Schinus terebinthifolia Raddi (Anacardiaceae), known as Brazilian pepper tree, stands out as a medicinal plant widely used in traditional medicine. The leaves are popularly used as anti-inflammatory agent and to relieve inflammatory conditions such as bronchitis, ulcers, and wounds, for example. AIM OF THE STUDY: The present study evaluated the acute toxicity, genotoxicity, and anti-inflammatory activity of S. terebinthifolia leaf lectin (SteLL) in mice (Mus musculus). MATERIALS AND METHODS: In the acute toxicity assay, the animals were treated intraperitoneally (i.p.) or orally (per os) with a single dose of 100 mg/kg. Genotoxicity was assessed by the comet and micronucleus assays. Carrageenan-induced peritonitis and paw edema models were used to evaluate the anti-inflammatory effects of SteLL (1, 5 and 10 mg/kg, i.p.). RESULTS: No animal died and no signs of intoxication or histopathological damage were observed in the acute toxicity assay. Genotoxic effect was not detected. In peritonitis assay, SteLL reduced in 56-69% leukocyte migration to the peritoneal cavity; neutrophil count decreased by 25-32%, while mononuclear cell count increased by 67-74%. SteLL promoted a notable reduction of paw edema after 4 h (61.1-63.4%). Morphometric analysis showed that SteLL also decreased the thickness of epidermal edema (30.2-40.7%). Furthermore, SteLL decreased MPO activity, plasma leakage, NO release, and modulated cytokines in both peritoneal fluid and paw homogenate. CONCLUSION: SteLL did not induce acute toxicity or genotoxicity in mice and stands out as a promising candidate in the development of new phytopharmaceuticals with anti-inflammatory action.

Urine Metabolites Enable Fast Detection of COVID-19 Using Mass Spectrometry.

The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need for particular reagents still exist. As an alternative diagnostic test, we present urine analysis through flow-injection-tandem mass spectrometry (FIA-MS/MS) as a powerful approach for COVID-19 diagnosis, targeting the detection of amino acids and acylcarnitines. We adapted a method that is widely used for newborn screening tests on dried blood for urine samples in order to detect metabolites related to COVID-19 infection. We analyzed samples from 246 volunteers with diagnostic confirmation via PCR. Urine samples were self-collected, diluted, and analyzed with a run time of 4 min. A Lasso statistical classifier was built using 75/25% data for training/validation sets and achieved high diagnostic performances: 97/90% sensitivity, 95/100% specificity, and 95/97.2% accuracy. Additionally, we predicted on two withheld sets composed of suspected hospitalized/symptomatic COVID-19-PCR negative patients and patients out of the optimal time-frame collection for PCR diagnosis, with promising results. Altogether, we show that the benchmarked FIA-MS/MS method is promising for COVID-19 screening and diagnosis, and is also potentially useful after the peak viral load has passed.

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1ß, IL-12/VEGF, and IL-10/IP-10 Axis.

BACKGROUND: Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. RESULTS: Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1ß, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. CONCLUSION: In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1ß, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1ß and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.

Tumor mixto Mülleriano heterólogo post radioterapia pelviana. Presentación de un caso / Malignant Heterologous Mixed Mullerian Tumor after pelvian radiotherapy. Case Presentation

Presentamos un caso de un paciente de 57 años de edad que presenta un tumor mixto mülleriano heterólogo 7 años post-radioterapia pelviana. Se efectuó anexohisterectomía total y posteriormente recibió 6 ciclos de quimioterapia con cisplatino y fosfamida. La paciente tuvo una rápida progresión, falleciendo un año luego del diagnóstico.Los tumores mixtos Müllerianos con áreas rabdomioblásticas se caracterizan por un comportamiento agresivo, resistencia al tratamiento y una evolución rápidamente fatal.Su diagnóstico histopatológico es muy importante por su implicancia diagnóstica