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International Journal of Molecular... Feb 2023Lower-than-normal platelet counts are a hallmark of the acquired autoimmune illness known as immune thrombocytopenia, which can affect both adults and children. Immune... (Review)
Review
Lower-than-normal platelet counts are a hallmark of the acquired autoimmune illness known as immune thrombocytopenia, which can affect both adults and children. Immune thrombocytopenia patients' care has evolved significantly in recent years, but the disease's diagnosis has not, and it is still only clinically achievable with the elimination of other causes of thrombocytopenia. The lack of a valid biomarker or gold-standard diagnostic test, despite ongoing efforts to find one, adds to the high rate of disease misdiagnosis. However, in recent years, several studies have helped to elucidate a number of features of the disease's etiology, highlighting how the platelet loss is not only caused by an increase in peripheral platelet destruction but also involves a number of humoral and cellular immune system effectors. This made it possible to identify the role of immune-activating substances such cytokines and chemokines, complement, non-coding genetic material, the microbiome, and gene mutations. Furthermore, platelet and megakaryocyte immaturity indices have been emphasized as new disease markers, and prognostic signs and responses to particular types of therapy have been suggested. Our review's goal was to compile information from the literature on novel immune thrombocytopenia biomarkers, markers that will help us improve the management of these patients.
Topics: Child; Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Blood Platelets; Megakaryocytes; Biomarkers
PubMed: 36901864
DOI: 10.3390/ijms24054438 -
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 -
Revue Medicale de Liege Mar 2020Psychomotor disadaptation syndrome (PDS) was first described by the Geriatrics School of Dijon (France), three decades ago, under the name «psychomotor regression...
Psychomotor disadaptation syndrome (PDS) was first described by the Geriatrics School of Dijon (France), three decades ago, under the name «psychomotor regression syndrome». Over time, the original clinical features remained unchanged. However, progress has been made in its pathophysiology understanding and care, hence the new name, PDS, appeared in the 1990s. The PDS is also called sub-cortico-frontal dysfunction syndrome since the 2000s. It corresponds to a decompensation of posture, gait and psychomotor automatisms, related to an alteration of the postural and motor programming, which is a consequence of sub-cortico-frontal lesions. The clinical features of PDS associate backward disequilibrium, nonspecific gait disorders and neurological signs (akinesia, reactional hypertonia, impaired reactive postural responses and protective reactions, etc.). Psychological disorders of PDS are a fear of standing and walking in its acute form (the post-fall syndrome), or a bradyphrenia and anhedonia in its chronic form. The PDS occurrence results from the combination of three factors implicated in the reduction in functional reserves related to the alteration of the sub-cortico-frontal structures: ageing, chronic afflictions and acute situations, which induce a decrease in cerebral blood flow. The PDS management must be multidisciplinary, including the physician, the physiotherapist, the psychologist, nurses and care assistants.
Topics: Accidental Falls; Adaptation, Physiological; France; Gait; Humans; Postural Balance; Posture; Sensation Disorders; Syndrome
PubMed: 32157844
DOI: No ID Found -
Laeknabladid Apr 2023For decades, breast implants have been available for breast reconstructions and breast augmentations to improve the patients' health-related quality of life. Silicone... (Review)
Review
For decades, breast implants have been available for breast reconstructions and breast augmentations to improve the patients' health-related quality of life. Silicone implants (SI) have been used since the middle of the last century for breast reconstruction, for example after breast cancer, for birth defects, gender confirmation procedures, or for breast augmentation. Every year, several hundred SI are performed in Iceland for these purposes, but no central register is maintained. It can be estimated that at least 1000 - 3000 women have SI in Iceland and that around 300 Icelandic patients get SI every year. This informal review article discusses the so-called ASIA syndrome, the immunological effects of silicone and the possible relationship of SI to autoimmune diseases, symptoms, and diagnosis. In the methodology, this paper does not rely on the strict conditions of systematic reviews, but the authors relied only on peer-reviewed sources through PubMed, UpToDate and Scopus. The keywords used are silicon, silicon implant, silicon particles, immune response, autoimmunity, autoinflammation, Autoimmune/inflammatory syndrome induced by aduvants, ASIA, ASIA syndrome, breast implant illness. The paper reviews known facts about the disease, its characteristics, and statistical aspects.
Topics: Humans; Female; Silicon; Quality of Life; Systematic Reviews as Topic; Breast Implants; Autoimmune Diseases; Silicones; Syndrome
PubMed: 36988131
DOI: 10.17992/lbl.2023.04.739 -
International Journal of Molecular... Mar 2021Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering...
Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering (activation step). The key feature of the triggering step is the activation of inflammasomes that are intracellular protein complexes consisting of pattern recognition receptors and inflammatory molecules. Inflammasomes are activated in response to various ligands, leading to the caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the gasdermin D-mediated pyroptosis, an inflammatory form of cell death. Previous studies have demonstrated that inflammasome activation is a key determinant of inflammatory responses and many human diseases; therefore, inflammasomes have been attracted much attention as critical drug targets to prevent and treat various human diseases.
Topics: Animals; Biomarkers; Disease; Flavonoids; Humans; Inflammasomes; Inflammation; Mice
PubMed: 33809447
DOI: 10.3390/ijms22063008 -
Frontiers in Physiology 2021Glucocorticoids, vertebrate steroid hormones produced by cells of the adrenal cortex or interrenal tissue, function dynamically to maintain homeostasis under constantly... (Review)
Review
Glucocorticoids, vertebrate steroid hormones produced by cells of the adrenal cortex or interrenal tissue, function dynamically to maintain homeostasis under constantly changing and occasionally stressful environmental conditions. They do so by binding and thereby activating nuclear receptor transcription factors, the Glucocorticoid and Mineralocorticoid Receptors (MR and GR, respectively). The GR, by virtue of its lower affinity for endogenous glucocorticoids (cortisol or corticosterone), is primarily responsible for transducing the dynamic signals conveyed by circadian and ultradian glucocorticoid oscillations as well as transient pulses produced in response to acute stress. These dynamics are important determinants of stress responsivity, and at the systemic level are produced by feedforward and feedback signaling along the hypothalamus-pituitary-adrenal/interrenal axis. Within receiving cells, GR signaling dynamics are controlled by the GR target gene and negative feedback regulator . Chronic stress can alter signaling dynamics imperfect physiological adaptation that changes systemic and/or cellular set points, resulting in chronically elevated cortisol levels and increased allostatic load, which undermines health and promotes development of disease. When this occurs during early development it can "program" the responsivity of the stress system, with persistent effects on allostatic load and disease susceptibility. An important question concerns the glucocorticoid-responsive gene regulatory network that contributes to such programming. Recent studies show that , a ubiquitously expressed GR target gene that encodes a Krüppel-like transcription factor important for metabolic plasticity and neuronal differentiation, is a feedforward regulator of GR signaling impacting cellular glucocorticoid responsivity, suggesting that it may be a critical node in that regulatory network.
PubMed: 34992551
DOI: 10.3389/fphys.2021.812195 -
Medicine Jul 2023As a multifactorial degenerative disease, Parkinson disease (PD) causes tremor, gait rigidity, and hypokinesia, which interfere with normal life. Because the disease is... (Review)
Review
As a multifactorial degenerative disease, Parkinson disease (PD) causes tremor, gait rigidity, and hypokinesia, which interfere with normal life. Because the disease is usually discovered in the late stage of complete degeneration of neurons, it can greatly delay treatment and even eventually lead to death. Therefore, the diagnosis of this disease is very challenging, and it is gratifying that substantial progress has been made in the development of optical coherence tomography (OCT) as a diagnostic biomarker for this disease, and genetic and imaging tests have become part of routine protocols in clinical practice. In the cognition of traditional Chinese medicine (TCM), this disease belongs to deficiency in origin and excess in superficiality, which is always caused by deficiency of liver and kidney, deficiency of qi and blood, and is closely related to wind, fire, phlegm and blood stasis. A large number of studies have shown that TCM can effectively treat motor and non-motor symptoms of PD, combat oxidative stress and reduce inflammatory response, and improve the quality of life of patients. Based on the pathophysiological mechanism of PD, this paper discusses the treatment of PD by TCM acupuncture combined with medicine based on syndrome differentiation.
Topics: Humans; Parkinson Disease; Quality of Life; Medicine, Chinese Traditional; Acupuncture Therapy; Syndrome
PubMed: 37505150
DOI: 10.1097/MD.0000000000034278 -
Molecular Immunology Dec 2021C1q is the recognition molecule of the classical pathway of the complement system. By binding to its targets, such as antigen-bound immunoglobulins or C-reactive... (Review)
Review
C1q is the recognition molecule of the classical pathway of the complement system. By binding to its targets, such as antigen-bound immunoglobulins or C-reactive protein, C1q contributes to the innate defense against infections. However, C1q also plays several other roles beyond its traditional role in complement activation. Circulating levels of C1q are determined in routine diagnostics as biomarker in several diseases. Decreased C1q levels are present in several autoimmune conditions. The decreased levels reflect the consumption of C1q by complement activation and serves as a biomarker for disease activity. In contrast, increased C1q levels are present in infectious and inflammatory diseases and may serve as a diagnostic biomarker. The increased levels of C1q are still incompletely understood but are suggested to modulate the adaptive immune response as C1q is known to impact on the maturation status of antigen-presenting cells and C1q impacts directly on T cells leading to decreased T-cell activity in high C1q conditions. In this review, we provide a comprehensive overview of the current literature on circulating levels of C1q in health and disease, and discuss how C1q can both protect against infections as well as maintain tolerance by regulating adaptive immunity.
Topics: Adaptive Immunity; Animals; Antibodies; Biomarkers; Complement C1q; Disease; Health; Humans
PubMed: 34735869
DOI: 10.1016/j.molimm.2021.10.010 -
International Journal of Molecular... May 2023Biallelic variants in , the gene encoding the lipid transporter ATP-binding cassette subfamily A member 3 (ABCA3) that is predominantly expressed in alveolar type II...
Biallelic variants in , the gene encoding the lipid transporter ATP-binding cassette subfamily A member 3 (ABCA3) that is predominantly expressed in alveolar type II cells, may cause interstitial lung diseases in children (chILD) and adults. Currently, there is no proven therapy, but, frequently, hydroxychloroquine (HCQ) is used empirically. We hypothesized that the in vitro responsiveness to HCQ might correlate to patients' clinical outcomes from receiving HCQ therapy. The clinical data of the subjects with chILD due to ABCA3 deficiency and treated with HCQ were retrieved from the literature and the Kids Lung Register data base. The in vitro experiments were conducted on wild type (WT) and 16 mutant ABCA3-HA-transfected A549 cells. The responses of the functional read out were assessed as the extent of deviation from the untreated WT. With HCQ treatment, 19 patients had improved or unchanged respiratory conditions, and 20 had respiratory deteriorations, 5 of whom transiently improved then deteriorated. The in vitro ABCA3 functional assays identified two variants with complete response, five with partial response, and nine with no response to HCQ. The variant-specific HCQ effects in vivo closely correlated to the in vitro data. An ABCA3 vesicle volume above 60% of the WT volume was linked to responsiveness to HCQ; the HCQ treatment response was concentration dependent and differed for variants in vitro. We generated evidence for an variant-dependent impact of the HCQ in vitro. This may also apply for HCQ treatment in vivo, as supported by the retrospective and uncontrolled data from the treatment of chILD due to ABCA3 deficiency.
Topics: Child; Humans; Hydroxychloroquine; Retrospective Studies; ATP-Binding Cassette Transporters; Lung; Lung Diseases, Interstitial; Mutation
PubMed: 37175887
DOI: 10.3390/ijms24098179 -
Cellular and Molecular Life Sciences :... Dec 2021Inflammation is vital to protect the host against foreign organism invasion and cellular damage. It requires tight and concise gene expression for regulation of pro- and... (Review)
Review
Inflammation is vital to protect the host against foreign organism invasion and cellular damage. It requires tight and concise gene expression for regulation of pro- and anti-inflammatory gene expression in immune cells. Dysregulated immune responses caused by gene mutations and errors in post-transcriptional regulation can lead to chronic inflammatory diseases and cancer. The mechanisms underlying post-transcriptional gene expression regulation include mRNA splicing, mRNA export, mRNA localisation, mRNA stability, RNA/protein interaction, and post-translational events such as protein stability and modification. The majority of studies to date have focused on transcriptional control pathways. However, post-transcriptional regulation of mRNA in eukaryotes is equally important and related information is lacking. In this review, we will focus on the mechanisms involved in the pre-mRNA splicing events, mRNA surveillance, RNA degradation pathways, disorders or symptoms caused by mutations or errors in post-transcriptional regulation during innate immunity especially toll-like receptor mediated pathways.
Topics: Animals; Disease; Humans; Immunity; Inflammation; Nonsense Mediated mRNA Decay; Pathogen-Associated Molecular Pattern Molecules; RNA
PubMed: 34971439
DOI: 10.1007/s00018-021-04073-5