Background
This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory ...pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)—derived exosomes, epithelial ovarian cancer (EOC)—derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome’s payload(s) upon its uptake and regulation of the TME.
Evidence
Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications.
Conclusion
Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.
Histamine and its receptors (H1R-H4R) play a crucial and significant role in the development of various allergic diseases. Mast cells are multifunctional bone marrow-derived tissue-dwelling cells ...that are the major producer of histamine in the body. H1R are expressed in many cells, including mast cells, and are involved in Type 1 hypersensitivity reactions. H2R are involved in Th1 lymphocyte cytokine production. H3R are mainly involved in blood-brain barrier function. H4R are highly expressed on mast cells where their stimulation exacerbates histamine and cytokine generation. Both H1R and H4R have important roles in the progression and modulation of histamine-mediated allergic diseases. Antihistamines that target H1R alone are not entirely effective in the treatment of acute pruritus, atopic dermatitis, allergic asthma, and other allergic diseases. However, antagonists that target H4R have shown promising effects in preclinical and clinical studies in the treatment of several allergic diseases. In the present review, we examine the accumulating evidence suggesting novel therapeutic approaches that explore both H1R and H4R as therapeutic targets for histamine-mediated allergic diseases.
In this paper, we present the potential of Explainable Artificial Intelligence methods for decision support in medical image analysis scenarios. Using three types of explainable methods applied to ...the same medical image data set, we aimed to improve the comprehensibility of the decisions provided by the Convolutional Neural Network (CNN). In vivo gastral images obtained by a video capsule endoscopy (VCE) were the subject of visual explanations, with the goal of increasing health professionals’ trust in black-box predictions. We implemented two post hoc interpretable machine learning methods, called Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP), and an alternative explanation approach, the Contextual Importance and Utility (CIU) method. The produced explanations were assessed by human evaluation. We conducted three user studies based on explanations provided by LIME, SHAP and CIU. Users from different non-medical backgrounds carried out a series of tests in a web-based survey setting and stated their experience and understanding of the given explanations. Three user groups (n = 20, 20, 20) with three distinct forms of explanations were quantitatively analyzed. We found that, as hypothesized, the CIU-explainable method performed better than both LIME and SHAP methods in terms of improving support for human decision-making and being more transparent and thus understandable to users. Additionally, CIU outperformed LIME and SHAP by generating explanations more rapidly. Our findings suggest that there are notable differences in human decision-making between various explanation support settings. In line with that, we present three potential explainable methods that, with future improvements in implementation, can be generalized to different medical data sets and can provide effective decision support to medical experts.
Thymic Stromal Lymphopoietin (TSLP) and Interleukin 33 (IL-33) are two cytokines released by cells that are in proximity to our environment, e.g., keratinocytes of the skin and epithelial cells of ...the airways. Pathogens, allergens, chemicals and other agents induce the release of TSLP and IL-33, which are recognized by mast cells. TSLP and IL-33 affect several mast cell functions, including growth, survival and mediator release. These molecules do not directly induce exocytosis, but cause release of de novo synthesized lipid mediators and cytokines. TSLP and IL-33 are also implicated in inflammatory diseases where mast cells are known to be an important part of the pathogenesis, e.g., asthma and atopic dermatitis. In this chapter we describe and discuss the implications of TSLP and IL-33 on mast cell functions in health and disease.
Interleukin‐33 (IL‐33) is a member of the interleukin‐1 (IL‐1) cytokine family. It is preferentially and constitutively expressed in different structural cells such as epithelial cells, endothelial ...cells, and smooth muscle cells. During necrosis of these cells (after tissue injury or cell damage), the IL‐33 that is released may be recognized by different types of immune cells, such as eosinophils, basophils and, especially, mast cells. IL‐33 needs the specific receptor ST2 (membrane‐bound receptor) and Interleukin‐1 receptor accessory protein heterodimer for its binding, which instigates the production of different types of cytokines and chemokines that have crucial roles in the exacerbation of allergic diseases and inflammation. IL‐33 and mast cells have been influentially associated to the pathophysiology of allergic diseases and inflammation. IL‐33 is a crucial regulator of mast cell functions and might be an attractive therapeutic target for the treatment of allergic and inflammatory diseases. In this review, we summarize the current knowledge regarding the roles of IL‐33 and mast cells in the pathogenesis of allergies and inflammation.
•SNPs in the IL-33 and IL-1RL1 genes play a crucial role in asthma and allergic diseases.•The IL-33/IL-1RL1 pathway modulates several functions in mast cells and basophils under physiological and ...pathological conditions.•Dysregulated activity of the IL-33/IL-1RL1 pathway could contribute to allergic disorders via altered functioning of mast cells and basophils.•Targeting the IL-33/IL-1RL1 pathway could form a novel therapeutic approach to treat allergic diseases.
Interleukin-33 (IL-33) is a recently discovered cytokine that belongs to the IL-1 superfamily and acts as an important regulator in several allergic disorders. It is considered to function as an alarmin, or danger cytokine, that is released upon structural cell damage. IL-33 activates several immune cells, including Th2 cells, mast cells and basophils, following its interaction with a cell surface heterodimer consisting of an IL-1 receptor-related protein ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP). This activation leads to the production of a variety of Th2-like cytokines that mediate allergic-type immune responses. Thus, IL-33 appears to be a double-edged sword because, in addition to its important contribution to host defence, it exacerbates allergic responses, such as allergic rhinitis and asthma. A major purported mechanism of IL-33 in allergy is the activation of mast cells to produce a variety of pro-inflammatory cytokines and chemokines. In this review, we summarize the current knowledge regarding the genetics and physiology of IL-33 and IL-1RL1 and its association with different allergic diseases by focusing on its effects on mast cells and basophils.
Context: Interleukin-33 and its receptor soluble suppression of tumorigenicity 2 (sST2) play an important role in inflammation and its role in periodontal disease is yet unclear. The role of both ...IL-33 and sST2 together in periodontal disease as biomarkers has never been studied. Aim: To assess the levels of IL-33 and sST2 in serum samples of patients with periodontitis and healthy subjects. Methods: A total of 71 subjects (30 healthy subjects and 41 patients with periodontal disease) were included in the cross-sectional study. Community Periodontal Index (CPI) was used to assess periodontal health by utilizing a mouth mirror and a CPI probe. Venous blood was collected and serum was separated. Serum levels of IL-33 and sST2 were determined by the enzyme-linked immunosorbent assay (ELISA) assay. Statistical Analysis: Graph Pad Prism 5 was used for statistical analysis. Mann Whitney test was applied to compare the two groups. Results: The level of IL-33 was not found to be elevated among healthy subjects and sST2 was found elevated among patients with periodontal disease. The serum concentration of IL-33 was found at 472 ± 114 pg/ml and 282 ± 77 pg/ml among healthy subjects and patients with periodontal disease respectively. Significantly higher values of sST2 at 28 ± 2 ng/ml were found among periodontal patients as compared to healthy subjects with values of 18 ± 1 ng/ml. No significant differences were noted between mild to moderate and severe periodontitis for IL-33 and sST2 between the two groups. Conclusion: This study shows alteration in serum levels of IL-33 and sST2 in periodontitis patients. IL-33 and sST2 may be potential inflammatory markers of periodontitis. Further studies are required on a large sample size for better understanding. This pilot study is the first to assess the serum levels of both IL-33 and sST2 together among patients with and without periodontal disease.
Reading Indian scene texts is complex due to the use of regional vocabulary, multiple fonts/scripts, and text size. This work investigates the significant differences in Indian and Latin Scene Text ...Recognition (STR) systems. Recent STR works rely on synthetic generators that involve diverse fonts to ensure robust reading solutions. We present utilizing additional non-Unicode fonts with generally employed Unicode fonts to cover font diversity in such synthesizers for Indian languages. We also perform experiments on transfer learning among six different Indian languages. Our transfer learning experiments on synthetic images with common backgrounds provide an exciting insight that Indian scripts can benefit from each other than from the extensive English datasets. Our evaluations for the real settings help us achieve significant improvements over previous methods on four Indian languages from standard datasets like IIIT-ILST, MLT-17, and the new dataset (we release) containing 440 scene images with 500 Gujarati and 2535 Tamil words. Further enriching the synthetic dataset with non-Unicode fonts and multiple augmentations helps us achieve a remarkable Word Recognition Rate gain of over 33% on the IIIT-ILST Hindi dataset. We also present the results of lexicon-based transcription approaches for all six languages.
Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell ...differentiation, proliferation, survival, migration, and angiogenesis. In the allergic diseases, alteration of S1P levels influences the differentiation and responsiveness of mast cells (MCs). S1P is synthesized by two sphingosine kinases (SphKs), sphingosine kinase 1, and sphingosine kinase 2. Engagement of IgE to the FcεRI receptor induces the activation of both the SphKs and generates S1P. Furthermore, SphKs are also essential to FcεRI-mediated MC activation. Activated MCs export S1P into the extracellular space and causes inflammatory response and tissue remodeling. S1P signaling has dual role in allergic responses. Activation of SphKs and secretion of S1P are required for MC activation; however, S1P signaling plays a vital role in the recovery from anaphylaxis. Several non-coding RNAs have been shown to play a crucial role in controlling the MC-associated inflammatory and allergic responses. Thus, S1P signaling pathway and its regulation by non-coding RNA could be explored as an exciting potential therapeutic target for asthma and other MC-associated diseases.
PDF
