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Nature Aug 2021The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile... (Review)
Review
The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile genetic elements that can move from one genomic location to another; in this process, they amplify and increase their presence in genomes, sometimes to very high copy numbers. In this Review we discuss new evidence and ideas that the activity of retrotransposons, a major subgroup of transposons overall, influences and even promotes the process of ageing and age-related diseases in complex metazoan organisms, including humans. Retrotransposons have been coevolving with their host genomes since the dawn of life. This relationship has been largely competitive, and transposons have earned epithets such as 'junk DNA' and 'molecular parasites'. Much of our knowledge of the evolution of retrotransposons reflects their activity in the germline and is evident from genome sequence data. Recent research has provided a wealth of information on the activity of retrotransposons in somatic tissues during an individual lifespan, the molecular mechanisms that underlie this activity, and the manner in which these processes intersect with our own physiology, health and well-being.
Topics: Aging; Animals; DNA Damage; Disease; Gene Silencing; Genome, Human; Genomics; Humans; Immunity, Innate; Retroelements
PubMed: 34349292
DOI: 10.1038/s41586-021-03542-y -
RNA (New York, N.Y.) Dec 2017RNA modifications have been historically considered as fine-tuning chemo-structural features of infrastructural RNAs, such as rRNAs, tRNAs, and snoRNAs. This view has... (Review)
Review
RNA modifications have been historically considered as fine-tuning chemo-structural features of infrastructural RNAs, such as rRNAs, tRNAs, and snoRNAs. This view has changed dramatically in recent years, to a large extent as a result of systematic efforts to map and quantify various RNA modifications in a transcriptome-wide manner, revealing that RNA modifications are reversible, dynamically regulated, far more widespread than originally thought, and involved in major biological processes, including cell differentiation, sex determination, and stress responses. Here we summarize the state of knowledge and provide a catalog of RNA modifications and their links to neurological disorders, cancers, and other diseases. With the advent of direct RNA-sequencing technologies, we expect that this catalog will help prioritize those RNA modifications for transcriptome-wide maps.
Topics: Animals; Disease; Humans; RNA; RNA Processing, Post-Transcriptional
PubMed: 28855326
DOI: 10.1261/rna.063503.117 -
Journal of Intensive Care Medicine Dec 2020Multiple organ dysfunction syndrome (MODS) is one of the most common syndromes of critical illness and the leading cause of mortality among critically ill patients....
Multiple organ dysfunction syndrome (MODS) is one of the most common syndromes of critical illness and the leading cause of mortality among critically ill patients. Multiple organ dysfunction syndrome is the clinical consequence of a dysregulated inflammatory response, triggered by clinically diverse factors with the main pillar of management being invasive organ support. During the last years, the advances in the clarification of the molecular pathways that trigger, mitigate, and determine the outcome of MODS have led to the increasing recognition of MODS as a distinct disease entity with distinct etiology, pathophysiology, and potential future therapeutic interventions. Given the lack of effective treatment for MODS, its early recognition, the early intensive care unit admission, and the initiation of invasive organ support remain the most effective strategies of preventing its progression and improving outcomes.
Topics: Critical Illness; Humans; Intensive Care Units; Multiple Organ Failure; Syndrome
PubMed: 31455133
DOI: 10.1177/0885066619871452 -
Advances in Experimental Medicine and... 2016Interleukin-6 (IL-6) is a prototypical cytokine with functional pleiotropy and plays an important role in host defense. When infections or tissue injuries occur, IL-6 is... (Review)
Review
Interleukin-6 (IL-6) is a prototypical cytokine with functional pleiotropy and plays an important role in host defense. When infections or tissue injuries occur, IL-6 is promptly produced by monocytes and macrophages and contributes to removal of infectious agents and restoration of damaged tissues through activation of immune, hematological, and acute-phase responses. Once stress is removed from the host, IL-6 synthesis ends, but uncontrolled excessive or persistent IL-6 production plays a pathological role in the development of various inflammatory diseases and cancers, indicating that IL-6 is a double-edged sword for the host. Thus, the proper IL-6 expression is very important for host defense and is strictly controlled by chromatin structure, transcriptional regulation, and posttranscriptional modification. Differentiation status of cells, various transcription factors, RNA-binding proteins, and microRNAs are involved in this process. Since it is assumed that dysregulation of any of these regulatory molecules may cause abnormal IL-6 expression in a particular disease, further elucidation of the factors and processes involved in IL-6 expression can be expected to facilitate to clarification of pathogenesis and to identification of novel target molecule(s) for specific diseases.
Topics: Animals; Disease; Gene Expression Regulation; Humans; Immune System; Inflammation; Interleukin-6; Protein Processing, Post-Translational; RNA Interference
PubMed: 27734409
DOI: 10.1007/978-94-024-0921-5_4 -
Journal of Clinical Rheumatology :... Sep 2023VEXAS ( V acuoles, E 1 enzyme, X -linked, A utoinflammatory, S omatic) syndrome is a newly identified disease caused by somatic mutations in the UBA1 gene resulting in... (Review)
Review
VEXAS ( V acuoles, E 1 enzyme, X -linked, A utoinflammatory, S omatic) syndrome is a newly identified disease caused by somatic mutations in the UBA1 gene resulting in refractory autoinflammatory features, frequently accompanied by cytopenias. Although the prevalence of this syndrome is yet unknown, understanding the clinical phenotype can assist clinicians in prompt recognition of cases among patients with glucocorticoid-responsive but immunosuppressive-resistant inflammatory symptoms. The pathophysiology, clinical presentation, diagnostic methods, treatment, and prognosis of VEXAS are herein reviewed.
Topics: Humans; Prognosis; Glucocorticoids; Immunosuppressive Agents; Myelodysplastic Syndromes; Syndrome; Mutation
PubMed: 36251488
DOI: 10.1097/RHU.0000000000001905 -
Proceedings of the National Academy of... Nov 2014Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet,...
Although major research efforts have focused on how specific components of foodstuffs affect health, relatively little is known about a more fundamental aspect of diet, the frequency and circadian timing of meals, and potential benefits of intermittent periods with no or very low energy intakes. The most common eating pattern in modern societies, three meals plus snacks every day, is abnormal from an evolutionary perspective. Emerging findings from studies of animal models and human subjects suggest that intermittent energy restriction periods of as little as 16 h can improve health indicators and counteract disease processes. The mechanisms involve a metabolic shift to fat metabolism and ketone production, and stimulation of adaptive cellular stress responses that prevent and repair molecular damage. As data on the optimal frequency and timing of meals crystalizes, it will be critical to develop strategies to incorporate those eating patterns into health care policy and practice, and the lifestyles of the population.
Topics: Circadian Rhythm; Disease; Eating; Health Status; Humans; Time Factors
PubMed: 25404320
DOI: 10.1073/pnas.1413965111 -
Nature Jan 2016In eukaryotic cells, the endoplasmic reticulum is essential for the folding and trafficking of proteins that enter the secretory pathway. Environmental insults or... (Review)
Review
In eukaryotic cells, the endoplasmic reticulum is essential for the folding and trafficking of proteins that enter the secretory pathway. Environmental insults or increased protein synthesis often lead to protein misfolding in the organelle, the accumulation of misfolded or unfolded proteins - known as endoplasmic reticulum stress - and the activation of the adaptive unfolded protein response to restore homeostasis. If protein misfolding is not resolved, cells die. Endoplasmic reticulum stress and activation of the unfolded protein response help to determine cell fate and function. Furthermore, endoplasmic reticulum stress contributes to the aetiology of many human diseases.
Topics: Animals; Disease; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Humans; Molecular Targeted Therapy; Protein Folding; Proteins; Unfolded Protein Response
PubMed: 26791723
DOI: 10.1038/nature17041 -
Molecules (Basel, Switzerland) Nov 2020Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation,... (Review)
Review
Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. In the current review, the anti-inflammation mechanisms of astaxanthin involved in targeting for inflammatory biomarkers and multiple signaling pathways, including PI3K/AKT, Nrf2, NF-κB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3, have been described. Furthermore, the applications of anti-inflammatory effects of astaxanthin in neurological diseases, diabetes, gastrointestinal diseases, hepatic and renal diseases, eye and skin disorders, are highlighted. In addition to the protective effects of astaxanthin in various chronic and acute diseases, we also summarize recent advances for the inconsistent roles of astaxanthin in infectious diseases, and give our view that the exact function of astaxanthin in response to different pathogen infection and the potential protective effects of astaxanthin in viral infectious diseases should be important research directions in the future.
Topics: Animals; Anti-Inflammatory Agents; Disease; Humans; Inflammation; Xanthophylls
PubMed: 33207669
DOI: 10.3390/molecules25225342 -
Biochimica Et Biophysica Acta.... Oct 2020One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in... (Review)
Review
One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in differentiation and activation processes of immune cells. Upon activation, immune cells have a high need for energy. Immune cells have different strategies to generate this energy. In pro-inflammatory cells, such as activated monocytes and activated T and B cells, the energy is generated by increasing glycolysis, while in regulatory cells, such as regulatory T cells or M2 macrophages, energy is generated by increasing mitochondrial function and beta-oxidation. Except for being important for energy supply during activation, mitochondria also induce immune responses. During an infection, they release mitochondrial danger associated molecules (DAMPs) that resemble structures of bacterial derived pathogen associated molecular patterns (PAMPs). Such mitochondrial DAMPS are for instance mitochondrial DNA with hypomethylated CpG motifs or a specific lipid that is only present in prokaryotic bacteria and mitochondria, i.e. cardiolipin. Via release of such DAMPs, mitochondria guide the immune response towards an inflammatory response against pathogens. This is an important mechanism in early detection of an infection and in stimulating and sustaining immune responses to fight infections. However, mitochondrial DAMPs may also have a negative impact. If mitochondrial DAMPs are released by damaged cells, without the presence of an infection, such as after a trauma, mitochondrial DAMPs may induce an undesired inflammatory response, resulting in tissue damage and organ dysfunction. Thus, immune cells have developed mechanisms to prevent such undesired immune activation by mitochondrial components. In the present narrative review, we will describe the current view of mitochondria in regulation of immune responses. We will also discuss the current knowledge on disturbed mitochondrial function in immune cells in various immunological diseases.
Topics: Animals; Autoimmune Diseases; B-Lymphocytes; DNA, Mitochondrial; Disease; Health; Humans; Immunity; Infections; Inflammation; Lymphocytes; Macrophages; Mitochondria; Monocytes; Pathogen-Associated Molecular Pattern Molecules; T-Lymphocytes
PubMed: 32473386
DOI: 10.1016/j.bbadis.2020.165845 -
Essays in Biochemistry Sep 2023Today, it is accepted that the ability to evade the attention of the immune system is an essential hallmark of cancer. Critically, as tumours progress, cancer cells can...
Today, it is accepted that the ability to evade the attention of the immune system is an essential hallmark of cancer. Critically, as tumours progress, cancer cells can protect themselves from the immune system's natural ability to fight the disease. This observation has led to an explosion of basic research to discover how to restore anti-tumour immunity for advancing cancer treatment. Clinical successes have been achieved following the approval of checkpoint inhibitor therapy to effectively prolong the life of many cancer patients with malignant disease. However, despite impressive survival gains, there is still a high variability of responses between different types of cancer and many patients still fail to respond. The disappointing findings that have been documented over the many clinical trials performed so far coincide with a much more complex view of immuno-oncology that has emerged from technological advances in functional fluorescent imaging techniques, high-throughput RNA sequencing and single-cell mass cytometry. The themed topic 'Immuno-Oncology' captures the contemporary understanding that individual tumours comprise remarkable mixtures of immune cell populations that actively contribute to neoplastic growth, invasion and metastasis through reciprocal and dynamic interactions with cancer cells. In the context of this new knowledge, the reviews discuss novel ideas of therapeutic opportunities for cancer. We would like to thank the authors for their excellent contributions.
Topics: Humans; Neoplasms; Syndrome
PubMed: 37767785
DOI: 10.1042/EBC20230071