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Trends in Genetics : TIG Dec 2019Adenosine-to-inosine (A-to-I) editing of RNA leads to deamination of adenosine to inosine. Inosine is interpreted as guanosine by the cellular machinery, thus altering... (Review)
Review
Adenosine-to-inosine (A-to-I) editing of RNA leads to deamination of adenosine to inosine. Inosine is interpreted as guanosine by the cellular machinery, thus altering the coding, folding, splicing, or transport of transcripts. A-to-I editing is tightly regulated. Altered editing has severe consequences for human health and can cause interferonopathies, neurological disorders, and cardiovascular disease, as well as impacting on cancer progression. ADAR1-mediated RNA editing plays an important role in antiviral immunity and is essential for distinguishing between endogenous and viral RNA, thereby preventing autoimmune disorders. Interestingly, A-to-I editing can be used not only to correct genomic mutations at the RNA level but also to modulate tumor antigenicity with large therapeutic potential. We highlight recent developments in the field, focusing on cancer and other human diseases.
Topics: Adenosine Deaminase; Animals; Disease Susceptibility; Drug Development; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Immunity; Isoenzymes; RNA Editing; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 31648814
DOI: 10.1016/j.tig.2019.09.004 -
Frontiers in Immunology 2019
Topics: Antigens, Neoplasm; Cancer Vaccines; Disease Management; Disease Susceptibility; Humans; Immunotherapy; Neoplasms
PubMed: 32010150
DOI: 10.3389/fimmu.2019.03117 -
Immunology Dec 2021
Topics: Cell Communication; Disease Susceptibility; Homeostasis; Humans; Immunity; Immunomodulation; Lymphocytes; Neutrophils
PubMed: 34725825
DOI: 10.1111/imm.13415 -
Viruses Jan 2021Although mobile genetic elements, or transposons, have played an important role in genome evolution, excess activity of mobile elements can have detrimental... (Review)
Review
Although mobile genetic elements, or transposons, have played an important role in genome evolution, excess activity of mobile elements can have detrimental consequences. Already, the enhanced expression of transposons-derived nucleic acids can trigger autoimmune reactions that may result in severe autoinflammatory disorders. Thus, cells contain several layers of protective measures to restrict transposons and to sense the enhanced activity of these "intragenomic pathogens". This review focuses on our current understanding of immunogenic patterns derived from the most active elements in humans, the retrotransposons long interspersed element (LINE)-1 and Alu. We describe the role of known pattern recognition receptors in nucleic acid sensing of LINE-1 and Alu and the possible consequences for autoimmune diseases.
Topics: Alu Elements; Animals; Disease Susceptibility; Genetic Predisposition to Disease; Host-Pathogen Interactions; Humans; Long Interspersed Nucleotide Elements; Retroelements
PubMed: 33445593
DOI: 10.3390/v13010094 -
Pediatrics and Neonatology Apr 2013
Topics: Disease Susceptibility; Female; Humans; Male; Sex Characteristics; Translational Research, Biomedical
PubMed: 23590948
DOI: 10.1016/j.pedneo.2013.02.001 -
Annals of Family Medicine 2008
Topics: Disease Susceptibility; Humans; Predictive Value of Tests; Probability; Risk Assessment; Stress, Psychological; Uncertainty
PubMed: 18474880
DOI: 10.1370/afm.848 -
Anesthesiology Jan 2018
Review
Topics: Anesthesia; Disease Susceptibility; Humans; Malignant Hyperthermia
PubMed: 28902673
DOI: 10.1097/ALN.0000000000001877 -
British Journal of Clinical Pharmacology Oct 2019The pharmacological effects of a drug depend on its concentration at the site of action, and therefore on the concentration in blood and on the dose. The relationship... (Review)
Review
The pharmacological effects of a drug depend on its concentration at the site of action, and therefore on the concentration in blood and on the dose. The relationship between the concentration or dose and the corresponding effect can usually be represented mathematically as a rectangular hyperbola; when effect is plotted against log concentration or log dose, the curve is sigmoidal. Inevitably, the effect size and the doses causing benefit and harm will differ among individuals, since they are biological phenomena: some individuals are more likely than others to suffer harm at any given dose. Some harmful effects can occur at much lower doses than those used in therapeutics; that is, the log dose-response curve for harm lies far to the left of the log dose-response curve for benefit. Those who suffer such reactions are hypersusceptible. When the dose-response curves for harm and therapeutic effect are in the same range, dose cannot separate the harmful effects from the therapeutic effects, and adverse reactions are collateral. Toxic effects occur when harmful doses are above the doses needed for benefit. In this review we consider factors that influence a subject's susceptibility to adverse drug reactions. Determinants of susceptibility include Immunological, Genetic, demographic (Age and Sex), Physiological and Exogenous factors (drug-drug interactions, for example), and Diseases and disorders such as renal failure, giving the mnemonic I GASPED. Some susceptibility factors are discrete (for example, all-or-none) and some are continuous; susceptibility can therefore be discrete or continuous; and the factors can interact to determine a person's overall susceptibility to harm.
Topics: Animals; Disease Susceptibility; Dose-Response Relationship, Drug; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease; Humans; Pharmaceutical Preparations
PubMed: 31169324
DOI: 10.1111/bcp.14015 -
Current Environmental Health Reports Sep 2020Arsenic is associated with cancer, heart disease, diabetes, and other outcomes that are also related to obesity. These similar effects raise the possibility that arsenic... (Review)
Review
PURPOSE OF REVIEW
Arsenic is associated with cancer, heart disease, diabetes, and other outcomes that are also related to obesity. These similar effects raise the possibility that arsenic plays a role in obesity causation. They also raise the possibility that obesity may be an important effect modifier of arsenic-caused disease. This review summarizes the complex relationship between arsenic and obesity, with an emphasis on current research from human studies.
RECENT FINDINGS
Experimental studies provide some evidence that arsenic could play a role in obesity pathogenesis. To date, however, these associations have not been confirmed in human studies. In contrast, several epidemiologic studies have shown that the risks of arsenic-caused disease are markedly higher in obese individuals, highlighting obesity as an important susceptibility factor. Arsenic exposure and obesity are prevalent and widespread. Research identifying vulnerable populations, including obese individuals, could lead to new interventions having broad public health effects.
Topics: Arsenic; Disease Susceptibility; Environmental Exposure; Humans; Obesity
PubMed: 32766950
DOI: 10.1007/s40572-020-00288-z -
Seminars in Immunopathology Mar 2019Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The... (Review)
Review
Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer's patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic immunity and susceptibility to a range of inflammatory diseases. The sexually dimorphic microbiome has been termed the 'microgenderome'. Herein, we review the evidence for the microgenderome and contemplate the role it plays in driving sex differences in immunity and disease susceptibility. We further consider the impact that biological sex might play in the response to treatments aimed at manipulating the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial transplant. These alternative therapies hold potential in the treatment of both psychological (e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) disorders differentially affecting males and females.
Topics: Animals; Disease Susceptibility; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Gonadal Steroid Hormones; Humans; Male; Peyer's Patches; Sex Characteristics
PubMed: 30298433
DOI: 10.1007/s00281-018-0716-7