Metabolomics in rheumatic diseases: desperately seeking biomarkers.
Ontology highlight
ABSTRACT:
SUBMITTER: Guma M
PROVIDER: S-EPMC4963238 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
Metabolomics in rheumatic diseases: desperately seeking biomarkers.
Guma Monica M Tiziani Stefano S Firestein Gary S GS
Nature reviews. Rheumatology 20160303 5
Metabolomics enables the profiling of large numbers of small molecules in cells, tissues and biological fluids. These molecules, which include amino acids, carbohydrates, lipids, nucleotides and their metabolites, can be detected quantitatively. Metabolomic methods, often focused on the information-rich analytical techniques of NMR spectroscopy and mass spectrometry, have potential for early diagnosis, monitoring therapy and defining disease pathogenesis in many therapeutic areas, including rheu ...[more]
Similar Datasets
Project description: Not available
| S-EPMC8789740 | biostudies-literature
Project description:MicroRNAs (miRNAs) are small non-coding single-stranded RNAs of about 22 nucleotides in length that act as post-transcriptional regulators of gene expression. Depending on the complementarity between miRNA and target mRNA, cleavage, destabilization, or translational suppression of mRNA occurs within the RISC (RNA-induced silencing complex). As gene expression regulators, miRNAs are involved in a variety of biological functions. Dysregulation of miRNAs and their target genes contribute to the pathophysiology of many diseases, including autoimmune and inflammatory disorders. MiRNAs are also present extracellularly in their stable form in body fluids. Their incorporation into membrane vesicles or protein complexes with Ago2, HDL, or nucleophosmin 1 protects them against RNases. Cell-free miRNAs can be delivered to another cell in vitro and maintain their functional potential. Therefore, miRNAs can be considered mediators of intercellular communication. The remarkable stability of cell-free miRNAs and their accessibility in body fluid makes them potential diagnostic or prognostic biomarkers and potential therapeutic targets. Here we provide an overview of the potential role of circulating miRNAs as biomarkers of disease activity, therapeutic response, or diagnosis in rheumatic diseases. Many circulating miRNAs reflect their involvement in the pathogenesis, while for plenty, their pathogenetic mechanisms remain to be explored. Several miRNAs described as biomarkers were also shown to be of therapeutic potential, and some miRNAs are already tested in clinical trials.
| S-EPMC10311055 | biostudies-literature
Project description:Objective. Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. Methods. HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. Results. Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. Conclusions. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF. A dose response design type examines the relationship between the size of the administered dose and the extent of the response of the organism(s). Using regression correlation
2006-01-24 | E-GEOD-4090 | biostudies-arrayexpress
Project description:There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.
| S-EPMC7203059 | biostudies-literature
Project description:The inherent complexity in the immune landscape of pediatric rheumatic disease necessitates a holistic system approach. Uncertainty in the mechanistic workings and etiological driving forces presents difficulty in personalized treatments. The development and progression of immunomics are well suited to deal with this complexity. Immunomics encompasses a spectrum of biological processes that entail genomics, transcriptomics, epigenomics, proteomics, and cytomics. In this review, we will discuss how various high dimensional technologies in immunomics have helped to grow a wealth of data that provide salient clues and biological insights into the pathogenesis of autoimmunity. Interfaced with critical unresolved clinical questions and unmet medical needs, these platforms have helped to identify candidate immune targets, refine patient stratification, and understand treatment response or resistance. Yet the unprecedented growth in data has presented both opportunities and challenges. Researchers are now facing huge heterogeneous data sets from different origins that need to be integrated and exploited for further data mining. We believe that the utilization and integration of these platforms will help unravel the complexities and expedite both discovery and validation of clinical targets.
| S-EPMC6558393 | biostudies-literature
Project description:Inflammatory rheumatic diseases (IRDs), encompassing a broad spectrum of chronic disorders, typically necessitate prolonged therapeutic intervention. Nevertheless, these diseases can sometimes manifest as severe emergencies requiring prompt and extensive medical intervention. Urgent intervention is essential for effectively recognizing and managing these situations, as they have the potential to be life-threatening and can result in severe morbidity and mortality. Emergencies in IRDs can occur with different frequencies and manifestations, including nervous system issues, severe infections, thrombosis-emboli, renal crises, gastrointestinal issues, and cardiovascular events. The fact that these events can occur across different IRDs underscores the necessity for heightened awareness and readiness among healthcare professionals. The pathophysiologic mechanisms that cause rheumatic emergencies are complex and involve multiple factors. These emergencies frequently arise due to the interplay between the inflammatory characteristics of rheumatic diseases and different systemic triggers. Early detection and treatment can have a substantial impact on an individual's prognosis in cases of severe and life-threatening disorders that require prompt recognition. Rapid decision-making and urgent care are required to effectively address rheumatic emergencies, as well as the implementation of a diagnostic flowchart. This article provides an overview of the emergencies linked to IRDs, classifying and assessing them individually. This article aims to enhance healthcare professionals' knowledge and awareness of critical situations by examining current recommendations and pathophysiological information. Implementing standardized diagnostic and treatment methods, providing patient education, and conducting continuing research into the underlying mechanisms are essential for enhancing the management of these critical situations and improving patient outcomes.
| S-EPMC11343811 | biostudies-literature
Project description:Interleukin-33 (IL-33) is a nuclear factor mainly expressed in barrier epithelium, endothelial cells, and fibroblast reticular cells. Some inflammatory cells also express IL-33 under certain conditions. The important role of IL-33 in allergic reactions, helminth infection, cancer, tissue fibrosis, chronic inflammation, organ transplantation, and rheumatic immune diseases has been extensively studied in recent years. IL-33 primarily activates various circulating and tissue-resident immune cells, including mast cell, group 2 innate lymphoid cell (ILC2), regulatory T cell (Treg), T helper 2 cell (Th2), natural killer cell (NK cell), and macrophage. Therefore, IL-33 plays an immunomodulatory role and shows pleiotropic activity in different immune microenvironments. The IL-33/serum stimulation-2 (ST2) axis has been shown to have a detrimental effect on rheumatoid arthritis, systemic lupus erythematosus, and other rheumatic diseases. Interestingly, IL-33 also plays a protective role in the repair of barrier epithelium and the activation of Tregs. Therefore, the role of IL-33/ST2 depends on the underlying pathological conditions in rheumatic diseases. This review focuses on the dual role of the IL-33/ST2 axis in rheumatic diseases.
| S-EPMC8473687 | biostudies-literature
Project description:Objective. Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. Methods. HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. Results. Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. Conclusions. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF. A dose response design type examines the relationship between the size of the administered dose and the extent of the response of the organism(s). Keywords: dose_response_design
2006-01-25 | GSE4090 | GEO
Project description:Rheumatology practice, during Coronavirus Disease 2019 (COVID-19) pandemic, has faced multifaceted challenges. Rheumatologists routinely prescribe immunosuppressant medications to their patients with multisystem autoimmune rheumatic diseases who are concerned about the increased risk of acquiring COVID-19 infection and are anxious to know if they should continue or hold these medications. Rheumatologists are often inundated by calls from their patients and physician colleagues caring for COVID-19 patients in hospitals, about how to manage the immunosuppression. Physicians face the challenging task of keeping up with the most up-to-date information on COVID-19. There are uncertainties about the mode of spread, clinical features, management options as well as long-term complications of COVID-19. Data are rapidly evolving and different studies on treatment options are showing contradictory results. It is known that viral illnesses can trigger a flare-up of underlying rheumatic disease that was previously in remission. To further complicate the scenario, some of the immunosuppressants have shown to have antiviral properties. This has created dilemma in the light of current COVID-19 crisis, as whether to continue or stop the immunosuppressive agents which could be essential to prevent complications of the rheumatic diseases including organ failure but also there is concern about acquiring COVID-19 or developing serious infection. Until we get an effective vaccine, immunosuppressant management for rheumatic diseases as well as other autoimmune diseases and transplants will pose difficult questions. This article is an attempt to review and understand COVID-19 and its impact on the immune system with special emphasis on managing medications used for autoimmune rheumatic diseases. We have provided general guidance about decision making, in regards to the immunosuppressive agents used in rheumatology practice with an understanding that this may change in near future.
| S-EPMC7476772 | biostudies-literature
Project description:Activation of the inflammasome, a protein complex responsible for many cellular functions, including the activation of the proinflammatory cytokines interleukin (IL)-1β and IL-18, has been identified as a key participant in many rheumatic diseases including autoimmune, inflammatory, and autoinflammatory syndromes. This review will discuss the recent advances in understanding the role of this complex in various rheumatic diseases. Furthermore, it will focus on available therapies, which directly and indirectly target the inflammasome and its downstream cytokines to quiet inflammation and possibly dampen autoimmune processes.
| S-EPMC4487391 | biostudies-literature