79 research outputs found
Mast cells as effector cells of innate immunity and regulators of adaptive immunity
No full textMast cells are widely distributed in human organs and tissues and they are particularly abundant at major body interfaces with the external environment such as the skin, the lung and the gastrointestinal tract. Moreover, mast cells are located around blood vessels and are highly represented within central and peripheral lymphoid organs. The strategic distribution of mast cells closely reflects the primary role of these cells in providing first-line defense against environmental dangers, in regulating local and systemic inflammatory reactions and in shaping innate and adaptive immune responses. Human mast cells have pleiotropic and multivalent functions that make them highly versatile cells able to rapidly adapt responses to microenvironmental changes. They express a wide variety of surface receptors including immunoglobulin receptors, pathogen-associated molecular pattern receptors and danger signal receptors. The abundance of these receptors makes mast cells unique and effective surveillance cells able to detect promptly aggression by viral, bacterial and parasitic agents. In addition, mast cells express multiple receptors for cytokines and chemokines that confer them the capacity of being recruited and activated at sites of inflammation. Once activated by immunological or nonimmunological stimuli mast cells secrete a wide spectrum of preformed (early) and de novo synthesized (late) mediators. Preformed mediators are stored within granules and are rapidly released in the extracellular environment to provide a fast vascular response that promotes inflammation and local recruitment of other innate immunity cells such as neutrophils, eosinophils, basophils and monocyte/macrophages. Later on, delayed release of multiple cytokines and chemokines from mast cells further induce modulation of cells of adaptive immunity and regulates tissue injury and, eventually, resolution of inflammation. Finally, mast cells express several costimulatory and inhibitory surface molecules that can finely tune activities of T cells, B cells and regulatory cells by cognate interactions within lymphoid organs. The multivalent capacity to recognize and to react to internal and external dangers together with their ability to cross-talk with other immunocompetent cells make mast cells a unique effector cell of innate responses and a main bridge between innate and adaptive immunity
EPR Spectroscopy Coupled with Spin Trapping as an Alternative Tool to Assess and Compare the Oxidative Stability of Vegetable Oils for Cosmetics
No full textAntioxidants are the most popular active ingredients in anti-aging cosmetics as they can restore the physiological radical balance and counteract the photoaging process. Instead of adding pure compounds into the formulations, some “precious” vegetable oils could be used due to their content of tocopherols, phenols, vitamins, etc., constituting a powerful antioxidant unsaponifiable fraction. Here, electron paramagnetic resonance (EPR) spectroscopy coupled with spin trapping was proven to provide a valid method for evaluating the antioxidant properties and the oxidative resistance of vegetable oils which, following UV irradiation, produce highly reactive radical species although hardly detectable. Extra virgin olive oil, sweet almond oil, apricot kernel oil, and jojoba oil were then evaluated by using N-t-butyl-α-phenylnitrone as a spin trapper and testing different UV irradiation times followed by incubation for 5 to 180 min at 70 °C. The EPR spectra were manipulated to obtain quantitative information useful for comparing the different tested samples. As a result, the knowledge acquired via the EPR analyses demonstrated jojoba oil as the best of the four considered oils in terms of both starting antioxidant ability and oxidative stability overtime. The obtained results confirmed the usefulness of the EPR spin trapping technique for the main proposed purpose
Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes
No full textAbnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p = 0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes
Risk Factors and Cofactors for Severe Anaphylaxis
No full textPurpose of review
Severe anaphylaxis is a generalized reaction in which cardiovascular and respiratory involvement lead to a fatal or near-fatal outcome. Triggers of severe anaphylaxis differ from one age group to another and are mostly represented by drugs and hymenoptera stings in adults and food in children. Several risk factors and cofactors can increase the odds of severe anaphylaxis by different and still undefined mechanisms.
Recent findings
Major risk factors for severe anaphylaxis include old age, male sex, and preexisting medical conditions such as mast cell disorders, cardiovascular diseases, and uncontrolled asthma. Antihypertensive drugs appear to increase the severity of anaphylaxis probably by impairing compensatory mechanism to support blood pressure during the reaction. Severe reactions are also associated with transient cofactors such as exercise following specific allergen exposure, treatment with nonsteroidal anti-inflammatory drugs, and alcohol consumption.
Summary
Identification of risk factors and potential concurrent cofactors for each individual patient is mandatory to prevent severe anaphylaxis. Risk stratification is crucial to develop personalized prevention strategies and action plans to avoid potentially life-threatening reactions
Flow mediated dilation shows impaired endothelial function in patients with mastocytosis
No full textMastocytosis is a rare disease characterized by clonal proliferation of mast cells in different organs. Clinical manifestations of mastocytosis are mostly due to the release of mediators from mast cells and, in many cases such as urticaria, flushing, angioedema and anaphylaxis, are expression of biological effects of mediators on endothelial cells. Chronic secretion of mediators in patients with mastocytosis may lead to alteration of endothelial function
Biomarkers for evaluation of mast cell and basophil activation
No full textMast cells and basophils play a pathogenetic role in allergic, inflammatory, and autoimmune disorders. These cells have different development, anatomical location and life span but share many similarities in mechanisms of activation and type of mediators. Mediators secreted by mast cells and basophils correlate with clinical severity in asthma, chronic urticaria, anaphylaxis, and other diseases. Therefore, effective biomarkers to measure mast cell and basophil activation in vivo could potentially have high diagnostic and prognostic values. An ideal biomarker should be specific for mast cells or basophils, easily and reproducibly detectable in blood or biological fluids and should be metabolically stable. Markers of mast cell and basophil include molecules secreted by stimulated cells and surface molecules expressed upon activation. Some markers, such as histamine and lipid mediators are common to mast cells and basophils whereas others, such as tryptase and other proteases, are relatively specific for mast cells. The best surface markers of activation expressed on mast cells and basophils are CD63 and CD203. While these mediators and surface molecules have been associated to a variety of diseases, none of them fulfills requirements for an optimal biomarker and search for better indicators of mast cell/basophil activation in vivo is ongoing
Adherence to Mediterranean Diet and its main determinants in a sample of Italian adults: results from the ARIANNA cross-sectional survey
No full textIntroduction: Over the last years, many Mediterranean countries, including Italy, have witnessed a shift away from the Mediterranean Diet, thus contributing to the high rates of overweight and obesity. The survey "Adherence to Mediterranean Diet in Italy (ARIANNA)" aimed to evaluate the Adherence to Mediterranean Diet (AMD) and its main determinants in the Italian population. Materials and methods: This study started on March 2023 and was addressed to adults aged >= 17 years, born and resident in Italy, proficient in Italian. Data are collected electronically through a voluntary, anonymous and self-administered questionnaire on the project website. Univariate and then multivariate logistic regressions were performed to evaluate associations between AMD and demographic characteristics, socio-economic status, health status, and lifestyle. Results: On a total of 3,732 completed questionnaires, the 87.70% of the respondents was female and the 71.28% was 17-40 years old. The 83.82% of the respondents had medium AMD, 11.33% low and only 4.85% high. The multivariate analysis revealed that being male (p 40 years (p < 0.05), workers (p <= 0.001), and unemployed (p < 0.05), determined the probability of having a lower AMD. Vegans and vegetarian's diets positively contributed to a higher AMD (p < 0.001). Discussion: These results highlighted a medium AMD in the Italian adult participants and suggested the necessity to implement tailored public health intervention strategies to improve food habits
The Algorithmic Horizon
No full textThis course outline was provided for student use. For a more detailed instructor version, and slide show presentation, please reach out to Mark Whitman at ([email protected]).In an era when decisions move faster than our ability to fully question them, The Algorithmic Horizon offers a timely call to pause and reflect on the systems we are building. Algorithms do not arrive preloaded with empathy or conscience; they come with logic, code, and the often-unexamined imprint of human priorities. This book is an invitation to examine those priorities, to challenge assumptions built into data-driven systems, and to lead with foresight and moral clarity. It asks us to slow down in our rush toward automation and consider the human stories behind the numbers. Dr. Whitman was indoctrinated in the Futures Research during his course of study at the Federal Bureau of Investigation National Academy, then as a police chief. The history and forebearers of futures research were introduced. Since then, Mark Whitman has reviewed much authors’ research on the topic. Diedra Cardamone is a skilled success coach in the CITE Center at Alfred State College. She has embraced methods through which she can engage students using practical applications of math. Diedra is a graduate from the Merchant Marine Academy and furthered her education at Harvard University achieving her graduate degree in Education. She underscores a key principle in education through her refrain to students, “We can’t make you good, you are already good, you are in college. We can only make you better!” Mark Whitman’s humility in the face of advanced technology is striking—he never forgets that behind every algorithm are the humans who designed it and those affected by it. In this work, Mark and his co-author Deidra Cardamone emphasize values often overlooked in technical texts: empathy, ethics, and curiosity. These principles are woven through every chapter, reminding even the most data-driven among us that successful innovation is as much about understanding people as it is about understanding code. The author’s motivation for writing this book shines through in its accessible tone and inclusive approach. This work, The Algorithmic Horizon, frequently recounts how many students and professionals are intimidated by statistics or years removed from the classroom, may shy away from learning about algorithms. That is exactly who this book welcomes. Mark and Deidra have crafted The Algorithmic Horizon to be a guide for the wary as well as the curious—a book that demystifies predictive analytics without ever talking down to the reader. By combining Mark’s expertise in AI and anomaly detection with Deidra’s experience in coaching and education, they have built a resource that meets learners where they are. This hypothesis is coupled with the team-teaching concept; in fact, multiple teachers may engage in the same course to provide horizons of thought not conceived during daily life. Second, as educators, the authors felt this may also provide deeper avenues of understanding between instructors of topical materials and engage thoughtful enthusiasm for student and instructor at the same time. What makes this book special is its heart. The Algorithmic Horizon does more than teach forecasting models or anomaly detection techniques; it encourages a mindset of thoughtful inquiry. The authors consistently highlight the importance of asking why and for whom an algorithm is designed. They prompt future leaders to be curious, to interrogate patterns rather than accept them at face value. In a world increasingly defined by automated decisions, this book asserts the importance of human judgment and ethical reflection at every step. I believe this book will be a beacon for students and professionals alike. It carries a message that our relationship with technology must be guided by understanding and responsibility. As you read on, you will find yourself equipped with new tools and frameworks—but more importantly, you will find the confidence to use them wisely. The Algorithmic Horizon hands you both the compass and the moral map for navigating a data-driven future. Enjoy the journey and prepare to see that the future of algorithms is not just about machines—it is about us.SUNY Alfred State CollegeMathematics and Physic
The circular RNA landscape in multiple sclerosis: Disease-specific associated variants and exon methylation shape circular RNA expression profile
No full textBACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs increasingly emerging as crucial actors in the pathogenesis of human diseases, including autoimmune and neurological disorders as multiple sclerosis (MS). Despite several efforts, the mechanisms regulating circRNAs expression are still largely unknown and the circRNA profile and regulation in MS-relevant cell models has not been completely investigated. In this work, we aimed at exploring the global landscape of circRNA expression in MS patients, also evaluating a possible correlation with their genetic and epigenetic background.
METHODS: We performed RNA-seq experiments on circRNA-enriched samples, derived from peripheral blood mononuclear cells (PBMCs) of 10 MS patients and 10 matched controls and performed differential circRNA expression. The genetic background was evaluated using array genotyping, and an expression quantitative trait loci (eQTL) analysis was carried out.
RESULTS: Expression analysis revealed 166 differentially expressed circRNAs in MS patients, 125 of which are downregulated. One of the top dysregulated circRNAs, hsa_circ_0007990, derives from the PGAP3 gene, encoding a protein relevant for the control of autoimmune responses. The downregulation of this circRNA was confirmed in two independent replication cohorts, suggesting its implementation as a possible RNA-based biomarker. The eQTL analysis evidenced a significant association between 89 MS-associated loci and the expression of at least one circRNA, suggesting that MS-associated variants could impact on disease pathogenesis by altering circRNA profiles. Finally, we found a significant correlation between exon methylation and circRNA expression levels, supporting the hypothesis that epigenetic features may play an important role in the definition of the cell circRNA pool.
CONCLUSION: We described the circRNA expression profile of PBMCs in MS patients, suggesting that MS-associated variants may tune the expression levels of circRNAs acting as circ-QTLs , and proposing a role for exon-based DNA methylation in regulating circRNA expression
Splicing-based biomarkers define a robust multigene classifier for relapsing-remitting multiple sclerosis
No full textBackground: Alternative splicing (AS) is recognized as a key mechanism in multiple sclerosis (MS). We aimed to construct and validate a multivariate AS-based classifier (MS-Splicing Score, MS-SS) for the discrimination of relapsing-remitting MS (RRMS) patients from healthy controls. Methods: Three AS events (IFNAR2 exon-8 skipping, NFAT5 exon-2 skipping, PRKCA exon-3∗ inclusion) were selected based on functional and literature evidence. Isoforms were quantified via fluorescent-competitive RT-PCR in peripheral blood RNA from two independent cohorts (Italy: 37 RRMS, 50 controls; USA: 29 RRMS, 20 controls). A logistic regression model was trained to derive the MS-SS, followed by ROC analysis. Results: The MS-SS distinguished RRMS patients from controls in both cohorts (Italy: p = 0.00083, AUC = 0.71, 95 %CI = 0.59–0.82; USA: p = 0.00074, AUC = 0.77, 95 %CI = 0.63–0.90). In the pooled dataset, the score remained significantly elevated in MS (p = 5.9 × 10−6, AUC = 0.72, 95 %CI = 0.64–0.81), and a PCA-based refinement improved classification accuracy, yielding an AUC = 0.87 (95 %CI = 0.81–0.94). At the optimal cutoff (Youden's index), the score achieved a sensitivity of 80 % and specificity of 86 %. Supervised rule-based modeling using a logic-learning machine algorithm identified interpretable splicing thresholds and enabled clinical classification at the individual level. Conclusion: Our study introduces a novel, robust AS-based classifier for RRMS and proposes a strategy for transcriptome-based biomarker development in neuroimmunology. However, the relatively small sample sizes within each cohort may limit the generalizability of these findings, warranting larger validation studies to confirm the clinical utility of this biomarker
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