-
Biochemia Medica Feb 2024YKL-40 or Chitinase-3-Like Protein 1 (CHI3L1) is a highly conserved glycoprotein that binds heparin and chitin in a non-enzymatic manner. It is a member of the chitinase... (Review)
Review
YKL-40 or Chitinase-3-Like Protein 1 (CHI3L1) is a highly conserved glycoprotein that binds heparin and chitin in a non-enzymatic manner. It is a member of the chitinase protein family 18, subfamily A, and unlike true chitinases, YKL-40 is a chitinase-like protein without enzymatic activity for chitin. Although its accurate function is yet unknown, the pattern of its expression in the normal and disease states suggests its possible engagement in apoptosis, inflammation and remodeling or degradation of the extracellular matrix. During an inflammatory response, YKL-40 is involved in a complicated interaction between host and bacteria, both promoting and attenuating immune response and potentially being served as an autoantigen in a vicious circle of autoimmunity. Based on its pathophysiology and mechanism of action, the aim of this review was to summarize research on the growing role of YKL-40 as a persuasive biomarker for inflammatory diseases' early diagnosis, prediction and follow-up ( cardiovascular, gastrointestinal, endocrinological, immunological, musculoskeletal, neurological, respiratory, urinary, infectious) with detailed structural and functional background of YKL-40.
Topics: Chitinase-3-Like Protein 1; Inflammation; Biomarkers; Disease; Research; Humans; Animals; Early Diagnosis
PubMed: 38125621
DOI: 10.11613/BM.2024.010502 -
Molecular Systems Biology Jan 2021A better understanding of the molecular mechanisms underlying disease is key for expediting the development of novel therapeutic interventions. Disease mechanisms are... (Review)
Review
A better understanding of the molecular mechanisms underlying disease is key for expediting the development of novel therapeutic interventions. Disease mechanisms are often mediated by interactions between proteins. Insights into the physical rewiring of protein-protein interactions in response to mutations, pathological conditions, or pathogen infection can advance our understanding of disease etiology, progression, and pathogenesis and can lead to the identification of potential druggable targets. Advances in quantitative mass spectrometry (MS)-based approaches have allowed unbiased mapping of these disease-mediated changes in protein-protein interactions on a global scale. Here, we review MS techniques that have been instrumental for the identification of protein-protein interactions at a system-level, and we discuss the challenges associated with these methodologies as well as novel MS advancements that aim to address these challenges. An overview of examples from diverse disease contexts illustrates the potential of MS-based protein-protein interaction mapping approaches for revealing disease mechanisms, pinpointing new therapeutic targets, and eventually moving toward personalized applications.
Topics: Disease; Gene Regulatory Networks; Humans; Mass Spectrometry; Protein Interaction Mapping
PubMed: 33434350
DOI: 10.15252/msb.20188792 -
Cells Oct 2019Cells need to exchange material and information with their environment. This is largely achieved via cell-surface receptors which mediate processes ranging from nutrient... (Review)
Review
Cells need to exchange material and information with their environment. This is largely achieved via cell-surface receptors which mediate processes ranging from nutrient uptake to signaling responses. Consequently, their surface levels have to be dynamically controlled. Endocytosis constitutes a powerful mechanism to regulate the surface proteome and to recycle vesicular transmembrane proteins that strand at the plasma membrane after exocytosis. For efficient internalization, the cargo proteins need to be linked to the endocytic machinery via adaptor proteins such as the heterotetrameric endocytic adaptor complex AP-2 and a variety of mostly monomeric endocytic adaptors. In line with the importance of endocytosis for nutrient uptake, cell signaling and neurotransmission, animal models and human mutations have revealed that defects in these adaptors are associated with several diseases ranging from metabolic disorders to encephalopathies. This review will discuss the physiological functions of the so far known adaptor proteins and will provide a comprehensive overview of their links to human diseases.
Topics: Adaptor Proteins, Signal Transducing; Animals; Clathrin-Coated Vesicles; Disease; Endocytosis; Health; Humans; Membrane Proteins; Models, Animal; Mutation
PubMed: 31671891
DOI: 10.3390/cells8111345 -
Exercise and Sport Sciences Reviews Jul 2018An interest has recently emerged in the role of circulating microRNAs (c-miRNAs) as posttranscriptional regulators, intercellular communicators and, especially, as... (Review)
Review
An interest has recently emerged in the role of circulating microRNAs (c-miRNAs) as posttranscriptional regulators, intercellular communicators and, especially, as potential biomarkers of the systemic response to acute exercise and training. We propose that, with the limited, heterogeneous, and mainly descriptive information currently available, c-miRNAs do not provide a reliable biomarker of exercise in healthy or diseased individuals.
Topics: Biomarkers; Disease; Exercise; Health; Humans; MicroRNAs
PubMed: 29659417
DOI: 10.1249/JES.0000000000000148 -
International Review of Cell and... 2015Aneuploidy is widely acknowledged as a leading cause of miscarriage and birth defects in humans, and is generally known to be deleterious to the survival of individual... (Review)
Review
Aneuploidy is widely acknowledged as a leading cause of miscarriage and birth defects in humans, and is generally known to be deleterious to the survival of individual cells. However, aneuploidy is also ubiquitous in cancer and is found to arise as an adaptive response in certain contexts. This dichotomy of aneuploidy has attracted the interest of researchers for over a century, but many studies have reached conflicting conclusions. The emergence of new technology has allowed scientists to revisit the aneuploidy problem and has fueled a number of recent studies aimed at understanding the effects of aneuploidy on cell physiology. Here, we review these studies, in light of previous observations and knowledge, specifically focusing on the effects of aneuploidy on cellular homeostasis, chromosome stability, and adaptation.
Topics: Adaptation, Physiological; Aneuploidy; Animals; Chromosomal Instability; Disease; Homeostasis; Humans
PubMed: 25708466
DOI: 10.1016/bs.ircmb.2014.11.002 -
Cognition & Emotion May 2024Previous studies found similarities in adults' disgust responses to benign (e.g. obesity) and actual disease signs (e.g. influenza). However, limited research has...
Previous studies found similarities in adults' disgust responses to benign (e.g. obesity) and actual disease signs (e.g. influenza). However, limited research has compared visual (i.e. benign and actual) to cognitive (i.e. disease label) disease cues in different age groups. The current study investigated disgust responses across middle childhood (7-9 years), late childhood (10-12 years), adolescence (13-17 years), and adulthood (18+ years). Participants viewed individuals representing a benign visual disease (obese), sick-looking (staphylococcus), sick-label (cold/flu), and healthy condition. Disgust-related outcomes were: (1) avoidance, or contact level with apparel the individual was said to have worn, (2) disgust facial reactions, and (3) a combination of (1) and (2). Avoidance was greater for the sick-looking and sick-label than the healthy and obese conditions. For facial reaction and combination outcomes, middle childhood participants responded with greater disgust to the sick-looking than the healthy condition, while late childhood participants expressed stronger disgust towards the sick-looking and obese conditions than the healthy condition. Adolescents and adults exhibited stronger disgust towards sick-label and sick-looking than obese and healthy conditions. Results suggest visual cues are central to children's disgust responses whereas adolescents and adult responses considered cognitive cues.
Topics: Humans; Adolescent; Female; Male; Child; Disgust; Young Adult; Adult; Facial Expression; Age Factors; Cues; Photic Stimulation; Disease
PubMed: 38349386
DOI: 10.1080/02699931.2023.2300390 -
Cell Death and Differentiation Dec 2016Most human genes encode multiple mRNA variants and protein products through alternative splicing of exons and introns during pre-mRNA processing. In this way,... (Review)
Review
Most human genes encode multiple mRNA variants and protein products through alternative splicing of exons and introns during pre-mRNA processing. In this way, alternative splicing amplifies enormously the coding potential of the human genome and represents a powerful evolutionary resource. Nonetheless, the plasticity of its regulation is prone to errors and defective splicing underlies a large number of inherited and sporadic diseases, including cancer. One key cellular process affected by alternative splicing is the programmed cell death or apoptosis. Many apoptotic genes encode for splice variants having opposite roles in cell survival. This regulation modulates cell and tissue homeostasis and is implicated in both developmental and pathological processes. Furthermore, recent evidence has also unveiled splicing-mediated regulation of genes involved in autophagy, another essential process for tissue homeostasis. In this review, we highlight some of the best-known examples of alternative splicing events involved in cell survival. Emphasis is given to the role of this regulation in human cancer and in the response to chemotherapy, providing examples of how alternative splicing of apoptotic genes can be exploited therapeutically.
Topics: Alternative Splicing; Animals; Apoptosis; Cell Survival; Disease; Homeostasis; Humans; Neoplasms
PubMed: 27689872
DOI: 10.1038/cdd.2016.91 -
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 -
Advances in Experimental Medicine and... 2014The acute inflammatory response is a complex defense mechanism that has evolved to respond rapidly to injury, infection, and other disruptions in homeostasis. This... (Review)
Review
The acute inflammatory response is a complex defense mechanism that has evolved to respond rapidly to injury, infection, and other disruptions in homeostasis. This robust responsiveness to biological stress likely endows the host with increased fitness, but over-robust or inadequate inflammation predisposes the host to various diseases. Importantly, well-compartmentalized inflammation is generally beneficial, but spillover of inflammation into the blood is a hallmark-and likely also a driver-of self-maintaining inflammation. The blood is also a key entry point and immunological interface for vectors of parasitic diseases, diseases that themselves incite systemic inflammation. The complex role of inflammation in health and disease has made this biological system difficult to understand comprehensively and modulate rationally for therapeutic purposes. Consequently, systems approaches have been applied in order to characterize dynamical properties and identify key control points in inflammation. This process begins with the collection of high-dimensional, experimental, and clinical data, followed by data reduction and data-driven modeling that finally informs mechanistic computational models for analysis, prediction, and rational modulation. These studies have suggested that the overall architecture of the inflammatory response includes a multiscale positive feedback from inflammation → tissue damage → inflammation, which is often inadequately controlled by negative feedback from anti-inflammatory mediators. Given the importance of the blood interface for the inflammatory response, and the accessibility of this compartment both as an immunological sampling reservoir for vectors as well as for diagnosis and therapy, we suggest that any rational efforts at modulating inflammation via the blood compartment must involve computational modeling.
Topics: Animals; Disease; Hemorrhage; Humans; Immunity, Innate; Inflammation; Models, Biological; Sepsis; Wounds and Injuries
PubMed: 25480644
DOI: 10.1007/978-1-4939-2095-2_11 -
Cellular & Molecular Immunology Mar 2011Nucleotide-binding oligomerization domain (NOD)-containing protein-like receptors (NLRs) are a recently discovered class of innate immune receptors that play a crucial... (Review)
Review
Nucleotide-binding oligomerization domain (NOD)-containing protein-like receptors (NLRs) are a recently discovered class of innate immune receptors that play a crucial role in initiating the inflammatory response following pathogen recognition. Some NLRs form the framework for cytosolic platforms called inflammasomes, which orchestrate the early inflammatory process via IL-1β activation. Mutations and polymorphisms in NLR-coding genes or in genetic loci encoding inflammasome-related proteins correlate with a variety of autoinflammatory diseases. Moreover, the activity of certain inflammasomes is associated with susceptibility to infections as well as autoimmunity and tumorigenesis. In this review, we will discuss how identifying the genetic characteristics of inflammasomes is assisting our understanding of both autoinflammatory diseases as well as other immune system-driven disorders.
Topics: Autoimmune Diseases; Cytokines; Disease; Health; Humans; Inflammasomes; Inflammation
PubMed: 21258359
DOI: 10.1038/cmi.2010.81