CD133 protein expression is observable in differentiated cells, stem cells, and progenitor cells within normal tissues, as well as in tumor tissues, including colorectal cancer cells. The CD133 protein is the predominant cell surface marker utilized to detect cancer cells exhibiting stem cell-like characteristics. CD133 alters common abnormal processes in colorectal cancer, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin pathways.
View Article and Find Full Text PDFTuft cells are more than guardian chemosensory elements of the digestive tract. They produce a variety of immunological effector molecules in response to stimulation; moreover, they are essential for defense against protozoa and nematodes. Beyond the description of their characteristics, this review aims to elucidate the potential pathogenic and therapeutic roles of colonic tuft cells in inflammatory bowel disease and colorectal cancer, focusing on their primarily immunomodulatory action.
View Article and Find Full Text PDFInflammasomes contribute to colorectal cancer signaling by primarily inducing inflammation in the surrounding tumor microenvironment. Its role in inflammation is receiving increasing attention, as inflammation has a protumor effect in addition to inducing tissue damage. The inflammasome's function is complex and controlled by several layers of regulation.
View Article and Find Full Text PDFBiomedicines
February 2024
Sirtuins (SIRTs) are stress-responsive proteins that regulate several post-translational modifications, partly by acetylation, deacetylation, and affecting DNA methylation. As a result, they significantly regulate several cellular processes. In essence, they prolong lifespan and control the occurrence of spontaneous tumor growth.
View Article and Find Full Text PDFGiven their fundamental physiological importance, their involvement in the immune system, and their close association with the development of intestinal diseases, the interest in intestinal epithelial cells has increased significantly over the past fifteen years. Their close association with intestinal worm and protozoan infections - a significant 2016 discovery - has further stimulated research into uncommon chemosensitive tuft epithelial cells. Although their numbers are relatively low, tuft cells are now recognized as an essential sentinel of the gastrointestinal tract, as their taste receptors for succinate, sweet, and bitter continuously monitor intestinal contents.
View Article and Find Full Text PDFGood's syndrome, an infrequent adult-onset immunodeficiency is characterized by the triad of thymoma, hypogammaglobulinemia, and increased susceptibility to recurrent infections. The clinical presentation is highly variable, with a spectrum ranging from recurrent bacterial and opportunistic infections to concomitant autoimmune diseases and, sometimes malignant pathologies. Due to heterogeneous clinical phenotypes and the lack of adequate diagnostic criteria, its recognition is often challenging, even delaying it by years.
View Article and Find Full Text PDFThe pervasive application of chimeric antigen receptor (CAR)-based cellular therapies in the treatment of oncological diseases has long been recognized. However, CAR T cells can target and eliminate autoreactive cells in autoimmune and immune-mediated diseases. By doing so, they can contribute to an effective and relatively long-lasting remission.
View Article and Find Full Text PDFGood syndrome is an infrequent and unique clinical entity of associated thymoma and immunodeficiency, first described almost 70 years ago. It is characterized by increased susceptibility to recurrent invasive bacterial and opportunistic infections as well as autoimmune and malignant diseases with an omnious prognosis. The affected patients are mainly middle-aged persons.
View Article and Find Full Text PDFThe immune system and autophagy share a functional relationship. Both innate and adaptive immune responses involve autophagy and, depending on the disease's origin and pathophysiology, it may have a detrimental or positive role on autoimmune disorders. As a "double-edged sword" in tumors, autophagy can either facilitate or impede tumor growth.
View Article and Find Full Text PDFBiomedicines
January 2023
Inflammatory processes and cancer stem cells (CSCs) are increasingly recognized as factors in the development of tumors. Emerging evidence indicates that CSCs are associated with cancer properties such as metastasis, treatment resistance, and disease recurrence. However, the precise interaction between CSCs and the immune microenvironment remains unexplored.
View Article and Find Full Text PDFThe basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders.
View Article and Find Full Text PDFWorld J Stem Cells
June 2022
In a recent article, the authors provide a detailed summary of the characteristics and biological functions of mesenchymal stem cells (MSCs), as well as a discussion on the potential mechanisms of action of MSC-based therapies. They describe the morphology, biogenesis, and current isolation techniques of exosomes, one of the most important fractions of the MSC-derived secretome. They also summarize the characteristics of MSC-derived exosomes and highlight their functions and therapeutic potential for tissue/organ regeneration and for kidney, liver, cardiovascular, neurological, and musculoskeletal diseases, as well as cutaneous wound healing.
View Article and Find Full Text PDFImmune-mediated inflammatory diseases (IMIDs) encompass several entities such as "classic" autoimmune disorders or immune-mediated diseases with autoinflammatory characteristics. Adult stem cells including mesenchymal stem cells (MSCs) are by far the most commonly used type in clinical practice. However, due to the possible side effects of MSC-based treatments, there is an increase in interest in the MSC-secretome (containing large extracellular vesicles, microvesicles, and exosomes) as an alternative therapeutic option in IMIDs.
View Article and Find Full Text PDFIn HT29 colon cancer cells, a close interplay between self-DNA-induced TLR9 signaling and autophagy response was found, with remarkable effects on cell survival and differentiation. IGF1R activation drives the development and malignant progression of colorectal cancer. IGF1R inhibition displays a controversial effect on autophagy.
View Article and Find Full Text PDFHGFR activation drives the malignant progression of colorectal cancer, and its inhibition displays anti-autophagic activity. The interrelated role of HGFR inhibition and TLR9/autophagy signaling in HT29 cancer cells subjected to modified self-DNA treatments has not been clarified. We analyzed this complex interplay with cell metabolism and proliferation measurements, TLR9, HGFR and autophagy inhibitory assays and WES Simple Western blot-based autophagy flux measurements, gene expression analyses, immunocytochemistry, and transmission electron microscopy.
View Article and Find Full Text PDFGut-associated lymphoid tissue is one of the most diverse and complex immune compartments in the human body. The subepithelial compartment of the gut consists of immune cells of innate and adaptive immunity, non-hematopoietic mesenchymal cells, and stem cells of different origins, and is organized into secondary (and even tertiary) lymphoid organs, such as Peyer's patches, cryptopatches, and isolated lymphoid follicles. The function of isolated lymphoid follicles is multifaceted; they play a role in the development and regeneration of the large intestine and the maintenance of (immune) homeostasis.
View Article and Find Full Text PDFPresence of cell-free DNA (cfDNA) in sera of patients with inflammatory bowel diseases (IBD) is a long-known fact. The biological effect of cfDNA administration on cellular autophagy within normal and inflammatory circumstances remains unclear. In this study, the effects of intravenous cfDNA pretreatment on autophagy response were studied in dextran sulfate sodium (DSS)-induced acute experimental colitis.
View Article and Find Full Text PDFThe purpose of regenerative medicine is to restore or enhance the normal function of human cells, tissues, and organs. From a clinical point of view, the use of stem cells is more advantageous than differentiated cells because they can be collected more easily and in larger quantities, their proliferation capacity is more pronounced, they are more resistant in cell culture, their aging is delayed, they are able to form a number of cell lines, and they are able to promote vascularization of tissue carriers. The therapeutic use of stem cells for disease modification, immunomodulation, or regenerative purposes are undoubtedly encouraging, but most studies are still in their early stages, and the clinical results reported are not clear with regard to therapeutic efficacy and potential side effects.
View Article and Find Full Text PDFIn relation of immunobiology, the consequence of the crosstalk between TLR9-signaling and autophagy is poorly documented in HT29 cancer cells. To assess the TLR9-mediated biologic effects of modified self-DNA sequences on cell kinetics and autophagy response HT29 cells were incubated separately with intact genomic (g), hypermethylated (m), fragmented (f), and hypermethylated/fragmented (m/f) self-DNAs. Cell viability, apoptosis, cell proliferation, colonosphere-formation were determined.
View Article and Find Full Text PDFPrimary immunodeficiencies consist of a group of genetically heterogeneous immune disorders affecting distinct elements of the innate and adaptive immune system. Patients with primary immunodeficiency are more prone to develop not only recurrent infections, but non-infectious complications, like inflammatory or granulomatous conditions, lymphoproliferative and solid malignancies, autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The concomitant appearance of primary immunodeficiency and autoimmunity appears to be rather paradoxical, therefore making the diagnosis of immunodeficiency patients with autoimmune complications challenging.
View Article and Find Full Text PDFWorld J Gastroenterol
December 2017
Metabolic syndrome (MetS), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor (IGF1R) signaling pathway. The IGF1R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context.
View Article and Find Full Text PDFComp Immunol Microbiol Infect Dis
June 2017
Background: The influence of cell-free DNA (fDNA) administration on the TLR9-autophagy regulatory crosstalk within inflammatory circumstances remains unclear.
Aims: To examine the immunobiologic effects of iv. fDNA injection on the TLR9-mediated autophagy response in murine DSS-colitis.
Malabsorption is a major and common clinical characteristics of short bowel syndrome (SBS) and inflammatory bowel diseases (IBD). Traditional treatment opportunities have focused on decreasing malabsorptive losses via dietary modifications and antisecretory/antidiarrheal agents. However, novel therapeutic modalities aim to enhance the absorptive capacity of the residual bowel by the administration of different intestinal growth factors including teduglutide.
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