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Romanian Journal of Morphology and... 2016Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies,... (Review)
Review
Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules. On the other hand, specific adaptive immune responses through high-affinity, class-switched IgG autoantibodies, which bind self-proteins, can cause tissue damage or malfunctions, inducing autoimmune diseases. The new technology that allows for more autoantibody screening may further enhance the clinical utility of autoantibody tests, making it possible to diagnose autoimmune disease in its early stages and to intervene before installing injuries. The aim of this review paper is to succinctly analyze the progress in the physiological role and regulatory significance of natural autoantibodies in health and disease.
Topics: Autoantibodies; Disease; Health; Humans; Neoplasms; Protective Agents
PubMed: 27833954
DOI: No ID Found -
Current Opinion in Immunology Feb 2020Recognition of invading pathogens and execution of defensive responses are crucial steps in successfully combating infectious diseases. Inflammasomes are a group of... (Review)
Review
Recognition of invading pathogens and execution of defensive responses are crucial steps in successfully combating infectious diseases. Inflammasomes are a group of diverse, signal-transducing complexes with key roles in both processes. While the responses mediated by inflammasomes are vital to host defense, aberrations in inflammasome regulation or activity can lead to the development of autoimmune and sterile inflammatory diseases, including cancer. The field of inflammasome research has rapidly expanded to identify novel regulatory pathways, new inflammasome components, and the mechanistic details of the activation of these complexes. In this review, we discuss recent insights into the regulation of inflammasomes by interferon regulatory factor proteins, newly discovered mechanisms of activation for the NLRP1b and NLRP6 inflammasomes, and recent studies exploring the viability of inflammasome-modulating immunotherapies.
Topics: Animals; Disease; Humans; Inflammasomes
PubMed: 31837596
DOI: 10.1016/j.coi.2019.11.007 -
Advances in Experimental Medicine and... 2016Signaling in tenocytes during development, homeostasis and injury involves multiple and redundant pathways. Given that tendons transmit mechanical forces from muscle to... (Review)
Review
Signaling in tenocytes during development, homeostasis and injury involves multiple and redundant pathways. Given that tendons transmit mechanical forces from muscle to bone to effect movement, a key function for tenocytes is the detection of and response to mechanical stimulation. Mechanotransduction involves matrix-integrin-cytoskeleton to nucleus signaling, gap junction intercellular communication, changes in intracellular calcium (Ca(2+)), activation of receptors and their pathways, and responses to biochemical factors such as hormones, growth factors, adenosine triphosphate (ATP) and its derivatives, and neuromodulators. The primary cilium also plays a key role in the detection of mechanical signals. During development, transforming growth factor-β (TGF-β), bone morphogenetic protein (BMP), and hedgehog (Hh) signaling modulate tendon differentiation and formation. The response to injury is complex and varied involving not only inflammatory mediators such as interleukin-1β but also mechanosensing. This chapter reviews the signaling pathways tenocytes use during mechanotransduction, development and in response to injury.
Topics: Animals; Cell Communication; Cell Physiological Phenomena; Disease; Humans; Mechanotransduction, Cellular; Signal Transduction; Stress, Mechanical; Tendons; Tenocytes; Wound Healing
PubMed: 27535250
DOI: 10.1007/978-3-319-33943-6_7 -
Abdominal Radiology (New York) Jan 2017Autoimmune hepatitis (AIH) is an uncommon, chronic inflammatory, and relapsing liver disease of unknown origin that may lead to liver cirrhosis, hepatocellular... (Review)
Review
Autoimmune hepatitis (AIH) is an uncommon, chronic inflammatory, and relapsing liver disease of unknown origin that may lead to liver cirrhosis, hepatocellular carcinoma, liver transplantation, or death. AIH occurs in all age groups and races but can frequently manifest as acute fulminant hepatitis. Clinical presentation of AIH can have features similar to primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC), and these diseases may coexist leading to overlap syndromes. Although histological diagnosis is necessary, imaging features often can demonstrate characteristics that may be helpful to distinguish these diseases. Imaging features of AIH are those of chronic liver disease, and imaging plays important role in detection of complications and ruling out other possible causes of chronic liver disease. Emerging techniques such as elastography provide non-invasive options for diagnosis of significant fibrosis and cirrhosis during clinical follow-up as well as assessment of response to treatment. In this study, we will describe imaging findings in AIH and overlap syndromes.
Topics: Diagnosis, Differential; Hepatitis, Autoimmune; Humans; Syndrome
PubMed: 27999888
DOI: 10.1007/s00261-016-1019-x -
Cold Spring Harbor Perspectives in... Jul 2014Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In... (Review)
Review
Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally.
Topics: Disease; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Precision Medicine
PubMed: 25059740
DOI: 10.1101/cshperspect.a008581 -
Biological & Pharmaceutical Bulletin 2017Secretory and membrane proteins are synthesized in ribosomes, then mature in the endoplasmic reticulum (ER), but if ER function is impaired, immature defective proteins... (Review)
Review
Secretory and membrane proteins are synthesized in ribosomes, then mature in the endoplasmic reticulum (ER), but if ER function is impaired, immature defective proteins accumulate in the ER. This situation is called ER stress: in response, a defensive mechanism called the unfolded protein response (UPR) is activated in cells to reduce the defective proteins. During the UPR, the ER transmembrane sensor molecules inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), and RNA-dependent protein kinase (PKR)-like ER kinase (PERK) are activated, stress signals are transduced to the outside of the ER, and various cell responses, including gene induction, occur. In ER-associated degradation (ERAD), one type of UPR, defective proteins are eventually expelled from the ER and degraded in the cytoplasm through the ubiquitin proteasome system. Since ER stress has been reported to have relationships with neurodegenerative diseases, diabetes, metabolic syndromes, and cancer, it is the focus of increased attention from the perspectives of elucidating pathogenic mechanisms, and in the development of therapeutics.
Topics: Animals; Disease; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Humans; Unfolded Protein Response
PubMed: 28867719
DOI: 10.1248/bpb.b17-00342 -
Pediatrics in Review Jul 2021
Topics: COVID-19; Child; Humans; SARS-CoV-2; Syndrome; Systemic Inflammatory Response Syndrome
PubMed: 34210761
DOI: 10.1542/pir.2020-004770 -
Epigenomics 2015Histone deacetylase (HDAC)6 is a member of the class IIb HDAC family. This enzyme is zinc-dependent and mainly localized in the cytoplasm. HDAC6 is a unique isoenzyme... (Review)
Review
Histone deacetylase (HDAC)6 is a member of the class IIb HDAC family. This enzyme is zinc-dependent and mainly localized in the cytoplasm. HDAC6 is a unique isoenzyme with two functional catalytic domains and specific physiological roles. Indeed, HDAC6 deacetylates various substrates including α-tubulin and HSP90α, and is involved in protein trafficking and degradation, cell shape and migration. Consequently, deregulation of HDAC6 activity was associated to a variety of diseases including cancer, neurodegenerative diseases and pathological autoimmune response. Therefore, HDAC6 represents an interesting potential therapeutic target. In this review, we discuss structural features of this histone deacetylase, regulation of its expression and activity, biological functions, implication in human disease initiation and progression. Finally will describe novel and selective HDAC6 inhibitors.
Topics: Animals; Disease; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Mice; Neoplasms
PubMed: 25687470
DOI: 10.2217/epi.14.69 -
Chemico-biological Interactions Nov 2016The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, cancer, chronic respiratory diseases, and neurological diseases. Together,... (Review)
Review
The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, cancer, chronic respiratory diseases, and neurological diseases. Together, they constitute the commonest cause of death and disability worldwide. Mitochondrial alterations, oxidative stress and inflammation underpin NCD and are molecular mechanisms playing major roles in the disease onset and natural history. Interrelations between the mechanisms of oxidative stress, inflammation and metabolism are, in the broadest sense of energy transformations, being increasingly recognized as part of the problem in NCD. Whether or not oxidative stress and inflammation are the causes or the consequences of cellular disturbances, they do significantly contribute to NCD. Paraoxonases are associated with mitochondria and mitochondria-associated membranes. They modulate mitochondria-dependent superoxide production, and prevent apoptosis. Their overexpression protects mitochondria from endoplasmic reticulum stress and subsequent mitochondrial dysfunction; highlighting that the anti-inflammatory effects of paraoxonases may be mediated, at least in part, by their protective role in mitochondria and associated organelle function. Since oxidative stress is implicated in the development of NCD (as a result of mitochondrial dysfunction), these data suggest that understanding the role and the molecular targets of paraoxonases may provide novel strategies of intervention in the treatment of these important diseases.
Topics: Animals; Aryldialkylphosphatase; Disease; Humans; Mitochondria; Models, Biological; Unfolded Protein Response
PubMed: 27062890
DOI: 10.1016/j.cbi.2016.04.005 -
Annual Review of Pathology 2015Inflammation, a vital response of the immune system to infection and damage to tissues, can be initiated by various germline-encoded innate immune-signaling receptors.... (Review)
Review
Inflammation, a vital response of the immune system to infection and damage to tissues, can be initiated by various germline-encoded innate immune-signaling receptors. Among these, the inflammasomes are critical for activation of the potent proinflammatory interleukin-1 cytokine family. Additionally, inflammasomes can trigger and maintain inflammatory responses aimed toward excess nutrients and the numerous danger signals that appear in a variety of chronic inflammatory diseases. We discuss our understanding of how inflammasomes assemble to trigger caspase-1 activation and subsequent cytokine release, describe how genetic mutations in inflammasome-related genes lead to autoinflammatory syndromes, and review the contribution of inflammasome activation to various pathologies arising from metabolic dysfunction. Insights into the mechanisms that govern inflammasome activation will help in the development of novel therapeutic strategies, not only for managing genetic diseases associated with overactive inflammasomes, but also for treating common metabolic diseases for which effective therapies are currently lacking.
Topics: Animals; Autoimmune Diseases; Humans; Inflammasomes; Inflammation; Syndrome
PubMed: 25423351
DOI: 10.1146/annurev-pathol-012414-040431