Epidemiological evidence associates chronic exposure to particulate matter (PM) with respiratory damage and lung cancer. Inhaled PM may induce systemic effects including inflammation and metastasis. ...This study evaluated whether PM induces expression of adhesion molecules in lung cancer cells promoting interaction with monocytes.
The expression of early and late adhesion molecules and their receptors was evaluated in A549 (human lung adenocarcinoma) cells using a wide range of concentrations of PM2.5 and PM10. Then we evaluated cellular adhesion between A549 cells and U937 (human monocytes) cells after PM exposure.
We found higher expression of both early and late adhesion molecules and their ligands in lung adenocarcinoma cells exposed to PM2.5 and PM10 particles present in the air pollution at Mexico City from 0.03 μg/cm2 with a statistically significant difference (p ≤ 0.05). PM10 had stronger effect than PM2.5. Both PM also stimulated cellular adhesion between tumor cells and monocytes.
This study reveals a comprehensive expression profile of adhesion molecules and their ligands upregulated by PM2.5 and PM10 in A549 cells. Additionally these particles induced cellular adhesion of lung cancer cells to monocytes. This highlights possible implications of PM in two cancer hallmarks i.e. inflammation and metastasis, underlying the high cancer mortality associated with air pollution.
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•Air pollutants upregulate adhesion molecules expression in lung adenocarcinoma.•Particulate matter increases adhesion between lung cancer cells and monocytes.•Strong cellular adhesion can promote inflammation and metastasis of lung cancer.
We identified the main changes in serum metabolites associated with severe (n = 46) and mild (n = 19) COVID-19 patients by gas chromatography coupled to mass spectrometry. The modified metabolic ...profiles were associated to an altered amino acid catabolism in hypoxic conditions. Noteworthy, three α-hydroxyl acids of amino acid origin increased with disease severity and correlated with altered oxygen saturation levels and clinical markers of lung damage. We hypothesize that the enzymatic conversion of α-keto-acids to α- hydroxyl-acids helps to maintain NAD recycling in patients with altered oxygen levels, highlighting the potential relevance of amino acid supplementation during SARS-CoV-2 infection.
SARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully ...elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.
Using a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.
The frequency of CD19
B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.
The severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.
B lymphocytes are recognized for their crucial role in the adaptive immunity since they represent the only leukocyte lineage capable of differentiating into Ab-secreting cells. However, it has been ...demonstrated that these lymphocytes can exert several Ab-independent functions, including engulfing and processing Ags for presentation to T cells, secreting soluble mediators, providing co-stimulatory signals, and even participating in lymphoid tissues development. Beyond that, several reports claiming the existence of multiple B cell subsets contributing directly to innate immune responses have appeared. These "innate-like" B lymphocytes, whose phenotype, development pathways, tissue distribution, and functions are in most cases notoriously different from those of conventional B cells, are crucial to early protective responses against pathogens by exerting "crossover" defensive strategies that blur the established boundaries of innate and adaptive branches of immunity. Examples of these mechanisms include the rapid secretion of the polyspecific natural Abs, increased susceptibility to innate receptors-mediated activation, cytokine secretion, downstream priming of other innate cells, usage of specific variable immunoglobulin gene-segments, and other features. As these new insights emerge, it is becoming preponderant to redefine the functionality of B cells beyond their classical adaptive-immune tasks.
Background
Most of the explanatory and prognostic models of COVID-19 lack of a comprehensive assessment of the wide COVID-19 spectrum of abnormalities. The aim of this study was to unveil novel ...biological features to explain COVID-19 severity and prognosis (death and disease progression).
Methods
A predictive model for COVID-19 severity in 121 patients was constructed by ordinal logistic regression calculating odds ratio (OR) with 95% confidence intervals (95% CI) for a set of clinical, immunological, metabolomic, and other biological traits. The accuracy and calibration of the model was tested with the area under the curve (AUC), Somer’s D, and calibration plot. Hazard ratios with 95% CI for adverse outcomes were calculated with a Cox proportional-hazards model.
Results
The explanatory variables for COVID-19 severity were the body mass index (BMI), hemoglobin, albumin, 3-Hydroxyisovaleric acid, CD8+ effector memory T cells, Th1 cells, low-density granulocytes, monocyte chemoattractant protein-1, plasma TRIM63, and circulating neutrophil extracellular traps. The model showed an outstanding performance with an optimism-adjusted AUC of 0.999, and Somer’s D of 0.999. The predictive variables for adverse outcomes in COVID-19 were severe and critical disease diagnosis, BMI, lactate dehydrogenase, Troponin I, neutrophil/lymphocyte ratio, serum levels of IP-10, malic acid, 3, 4 di-hydroxybutanoic acid, citric acid, myoinositol, and cystine.
Conclusions
Herein, we unveil novel immunological and metabolomic features associated with COVID-19 severity and prognosis. Our models encompass the interplay among innate and adaptive immunity, inflammation-induced muscle atrophy and hypoxia as the main drivers of COVID-19 severity.
B lymphocytes are a leukocyte subset capable of developing several functions apart from differentiating into antibody‐secreting cells. These processes are triggered by external activation signals ...that induce changes in the plasma membrane properties, regulated by the formation of different lipid‐bilayer subdomains that are associated with the underlying cytoskeleton through different linker molecules, thus allowing the functional specialization of regions within the membrane. Among these, there are tetraspanin‐enriched domains. Tetraspanins constitute a superfamily of transmembrane proteins that establish lateral associations with other molecules, determining its activity and localization. In this study, we identified TSPAN33 as an active player during B‐lymphocyte cytoskeleton and plasma membrane‐related phenomena, including protrusion formation, adhesion, phagocytosis, and cell motility. By using an overexpression model of TSPAN33 in human Raji cells, we detected a specific distribution of this protein that includes membrane microvilli, the Golgi apparatus, and extracellular vesicles. Additionally, we identified diminished phagocytic ability and altered cell adhesion properties due to the aberrant expression of integrins. Accordingly, these cells presented an enhanced migratory phenotype, as shown by its augmented chemotaxis and invasion rates. When we evaluated the mechanic response of cells during fibronectin‐induced spreading, we found that TSPAN33 expression inhibited changes in roughness and membrane tension. Contrariwise, TSPAN33 knockdown cells displayed opposite phenotypes to those observed in the overexpression model. Altogether, our data indicate that TSPAN33 represents a regulatory element of the adhesion and migration of B lymphocytes, suggesting a novel implication of this tetraspanin in the control of the mechanical properties of their plasma membrane.
Tetraspanins constitute a superfamily of transmembrane proteins that establish lateral associations with other molecules, determining its activity and localization. In this study, we identified the last described member of this family, tetraspanin 33 (TSPAN33), as an active player during B‐lymphocyte cytoskeleton and plasma membrane‐related phenomena, including protrusion formation, adhesion, phagocytosis, and cell motility.
Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE), characterized by abnormal B cell activation and differentiation to memory or plasma effector ...cells. However, the role of these cells in the pathogenesis of LN is not fully understood, as well as the effect of induction therapy on B cell subsets, possibly associated with this manifestation, like aged-associated B cells (ABCs). Consequently, we analyzed the molecules defining the ABCs subpopulation (CD11c, T-bet, and CD21) through flow cytometry of blood samples from patients with lupus presenting or not LN, following up a small sub-cohort after six months of induction therapy. The frequency of ABCs resulted higher in LN patients compared to healthy subjects. Unexpectedly, we identified a robust reduction of a CD21
hi
subset that was almost specific to LN patients. Moreover, several clinical and laboratory lupus features showed strong and significant correlations with this undefined B cell subpopulation. Finally, it was observed that the induction therapy affected not only the frequencies of ABCs and CD21
hi
subsets but also the phenotype of the CD21
hi
subset that expressed a higher density of CXCR5. Collectively, our results suggest that ABCs, and more importantly the CD21
hi
subset, may work to assess therapeutic response since the reduced frequency of CD21
hi
cells could be associated with the onset of LN.
El presente artículo evalúa la situación de la educación básica en las repúblicas de México y Colombia, a raíz de la emergencia sanitaria causada por el Covid-19. La investigación se desarrolló a ...través del método analítico-sintético, bajo el paradigma holístico de investigación, que permitió la comprensión del fenómeno estudiado mediante técnicas e instrumentos de análisis y comparación de datos. En ambos países se observan desigualdades en materia de acceso a la educación, causadas en especial por la falta de servicios y herramientas digitales y la falta de conocimiento del uso de las nuevas tecnologías por parte de estudiantes y maestros. Lo anterior se convierte en una limitante del progreso, de los cambios sociales y en causal de un mayor distanciamiento de la esperada justicia social, imposibilitando percibir, difundir y respetar los derechos humanos y brindar alta calidad educativa a las nuevas generaciones de ciudadanos.
Immunoglobulin A (IgA) is the main antibody isotype in body fluids such as tears, intestinal mucous, colostrum, and saliva. There are two subtypes of IgA in humans: IgA1, mainly present in blood and ...mucosal sites, and IgA2, preferentially expressed in mucosal sites like the colon. In clinical practice, immunoglobulins are typically measured in venous or capillary blood; however, alternative samples, including saliva, are now being considered, given their non-invasive and easy collection nature. Several autoimmune diseases have been related to diverse abnormalities in oral mucosal immunity, such as rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus (SLE).
We decided to evaluate the levels of both IgA subtypes in the saliva of SLE patients. A light chain capture-based ELISA measured specific IgA1 and IgA2 levels in a cohort of SLE patients compared with age and gender-matched healthy volunteers.
Surprisingly, our results indicated that in the saliva of SLE patients, total IgA and IgA1 subtype were significantly elevated; we also found that salivary IgA levels, particularly IgA2, positively correlate with anti-dsDNA IgG antibody titers. Strikingly, we also detected the presence of salivary anti-nucleosome IgA antibodies in SLE patients, a feature not previously reported elsewhere.
According to our results and upon necessary validation, IgA characterization in saliva could represent a potentially helpful tool in the clinical care of SLE patients with the advantage of being a more straightforward, faster, and safer method than manipulating blood samples.
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