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Cell Host & Microbe May 2015Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease... (Review)
Review
Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.
Topics: Anti-Bacterial Agents; Child; Disease; Dysbiosis; Humans; Infant; Microbiota
PubMed: 25974298
DOI: 10.1016/j.chom.2015.04.006 -
Molecular Aspects of Medicine Apr 2017The regulation of gene expression in response to environmental and behavioural cues is critical for many biological processes. Histone tail modifications are dynamic... (Review)
Review
The regulation of gene expression in response to environmental and behavioural cues is critical for many biological processes. Histone tail modifications are dynamic and, as such, can regulate gene expression in response to extracellular conditions. Many of the enzymes involved in adding and removing these modifications require cofactors that are products of intermediary metabolism pathways, thus linking cellular metabolism to the regulation of gene expression. Furthermore, the expression and activity of such enzymes are influenced by the cellular concentrations of metabolic products. Under- and over-nutrition can induce epigenetic changes that influence chromatin structure and define a metabolic program. Importantly, recent studies have demonstrated that such changes during the pre- and peri-natal periods can be long-lasting, influencing the disease risk later in life and could be transmitted to subsequent generations. Moreover, damaging gene expression patterns observed in metabolic diseases such as diabetes are driven by persistent changes in chromatin structure, raising the possibility of targeting epigenetic pathways for the treatment of disease.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; Disease; Glucose; Health; Humans; Protein Processing, Post-Translational
PubMed: 27697603
DOI: 10.1016/j.mam.2016.09.004 -
Sleep Medicine Clinics Jun 2023Control of breathing in children varies with age and sleep state. There is overlap between central hypoventilation, autonomic dysfunction, and hypothalamic dysfunction... (Review)
Review
Control of breathing in children varies with age and sleep state. There is overlap between central hypoventilation, autonomic dysfunction, and hypothalamic dysfunction in the rare disorders (congenital central hypoventilation syndrome and rapid-onset obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysregulation). Other, more common disorders that typically present in childhood also include central hypoventilation and disordered ventilatory responses.
Topics: Child; Humans; Hypoventilation; Syndrome; Obesity; Sleep Apnea, Central; Autonomic Nervous System Diseases
PubMed: 37120159
DOI: 10.1016/j.jsmc.2023.01.002 -
Cellular & Molecular Immunology Apr 2018For the past twenty years, chemokines have emerged as a family of critical mediators of cell migration during immune surveillance, development, inflammation and cancer... (Review)
Review
For the past twenty years, chemokines have emerged as a family of critical mediators of cell migration during immune surveillance, development, inflammation and cancer progression. Chemokines bind to seven transmembrane G protein-coupled receptors (GPCRs) that are expressed by a wide variety of cell types and cause conformational changes in trimeric G proteins that trigger the intracellular signaling pathways necessary for cell movement and activation. Although chemokines have evolved to benefit the host, inappropriate regulation or utilization of these small proteins may contribute to or even cause diseases. Therefore, understanding the role of chemokines and their GPCRs in the complex physiological and diseased microenvironment is important for the identification of novel therapeutic targets. This review introduces the functional array and signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as their roles in homeostasis, inflammation, immune responses and cancer.
Topics: Animals; Chemokines; Disease; Homeostasis; Humans; Inflammation; Ligands; Receptors, G-Protein-Coupled
PubMed: 29375126
DOI: 10.1038/cmi.2017.134 -
Cells Oct 2021Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their... (Review)
Review
Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their role in remodelling the extracellular matrix, however more recently they have been recognised as a functionally highly diverse cell population that constantly responds and adapts to their environment. Biological memory is the process of a sustained altered cellular state and functions in response to a transient or persistent environmental stimulus. While it is well established that fibroblasts retain a memory of their anatomical location, how other environmental stimuli influence fibroblast behaviour and function is less clear. The ability of fibroblasts to respond and memorise different environmental stimuli is essential for tissue development and homeostasis and may become dysregulated in chronic disease conditions such as fibrosis and cancer. Here we summarise the four emerging key areas of fibroblast adaptation: positional, mechanical, inflammatory, and metabolic memory and highlight the underlying mechanisms and their implications in tissue homeostasis and disease.
Topics: Disease; Embryonic Development; Fibroblasts; Homeostasis; Humans; Inflammation; Models, Biological
PubMed: 34831065
DOI: 10.3390/cells10112840 -
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 -
FEBS Letters Nov 2014While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to... (Review)
Review
While our genomes are essentially static, our microbiomes are inherently dynamic. The microbial communities we harbor in our bodies change throughout our lives due to many factors, including maturation during childhood, alterations in our diets, travel, illnesses, and medical treatments. Moreover, there is mounting evidence that our microbiomes change us, by promoting health through their beneficial actions or by increasing our susceptibility to diseases through a process termed dysbiosis. Recent technological advances are enabling unprecedentedly detailed studies of the dynamics of the microbiota in animal models and human populations. This review will highlight key areas of investigation in the field, including establishment of the microbiota during early childhood, temporal variability of the microbiome in healthy adults, responses of the microbiota to intentional perturbations such as antibiotics and dietary changes, and prospective analyses linking changes in the microbiota to host disease status. Given the importance of computational methods in the field, this review will also discuss issues and pitfalls in the analysis of microbiome time-series data, and explore several promising new directions for mathematical model and algorithm development.
Topics: Aging; Animals; Computational Biology; Disease; Environment; Humans; Microbiota; Models, Biological
PubMed: 24583074
DOI: 10.1016/j.febslet.2014.02.037 -
Cell Biology and Toxicology Apr 2017Autophagy is a lysosomal degradation pathway of eukaryotic cells that is highly conserved from yeast to mammals. During this process, cooperating protein complexes are... (Review)
Review
Autophagy is a lysosomal degradation pathway of eukaryotic cells that is highly conserved from yeast to mammals. During this process, cooperating protein complexes are recruited in a hierarchic order to the phagophore assembly site (PAS) to mediate the elongation and closure of double-membrane vesicles called autophagosomes, which sequester cytosolic components and deliver their content to the endolysosomal system for degradation. As a major cytoprotective mechanism, autophagy plays a key role in the stress response against nutrient starvation, hypoxia, and infections. Although numerous studies reported that impaired function of core autophagy proteins also contributes to the development and progression of various human diseases such as neurodegenerative disorders, cardiovascular and muscle diseases, infections, and different types of cancer, the function of this process in human diseases remains unclear. Evidence often suggests a controversial role for autophagy in the pathomechanisms of these severe disorders. Here, we provide an overview of the molecular mechanisms of autophagy and summarize the recent advances on its function in human health and disease.
Topics: Animals; Autophagosomes; Autophagy; Disease; Humans; Models, Biological; Translational Research, Biomedical
PubMed: 27957648
DOI: 10.1007/s10565-016-9374-5 -
Zeitschrift Fur Rheumatologie Apr 2023Paraneoplastic syndromes in rheumatology are a group of canonical rare rheumatic diseases with musculoskeletal involvement that occur in close temporal and causal... (Review)
Review
Paraneoplastic syndromes in rheumatology are a group of canonical rare rheumatic diseases with musculoskeletal involvement that occur in close temporal and causal association with malignancies. Knowledge of these possibly enables a prognostically relevant early diagnosis of the underlying malignant disease. In the era of immune checkpoint inhibitor treatment, there are first indications of an increase in the incidence and severity of paraneoplastic syndromes, so that they are becoming of increasing importance for the practicing rheumatologist. These nine syndromes, paraneoplastic arthritis, palmar fasciitis and polyarthritis, remitting seronegative symmetrical synovitis with pitting edema, pancreatic panniculitis with polyarthritis, paraneoplastic vasculitis, cancer-associated myositis, hypertrophic osteoarthropathy (Marie-Bamberger), eosinophilic fasciitis and tumor-induced osteomalacia, usually occur with characteristic courses and sometimes pathognomonic clinical manifestations, which are presented in this article accompanied by the rational use of a diagnostic algorithm for tumor detection. With frequently disappointing therapeutic response to glucocorticoids, nonsteroidal antirheumatic drugs and immunosuppressants, treatment of the underlying malignant disease represents the crucial step in the treatment of paraneoplastic syndromes.
Topics: Humans; Rheumatic Diseases; Rheumatology; Early Detection of Cancer; Paraneoplastic Syndromes; Synovitis; Neoplasms; Arthritis; Syndrome
PubMed: 36690750
DOI: 10.1007/s00393-022-01314-1 -
Health Psychology Review Dec 2019Research on the Commonsense Self-Regulation Model has emphasised reflective/conscious perceptual processes regarding illness threat (beliefs about symptoms,... (Review)
Review
Research on the Commonsense Self-Regulation Model has emphasised reflective/conscious perceptual processes regarding illness threat (beliefs about symptoms, consequences, timeline, and curability) in predicting and changing coping behaviours. Understanding of illness self-regulation and avenues for intervention might be enriched by consideration of automatic processes that influence the recognition and identification of illness, response to illness, and ongoing management. This article adopts an integrative approach to (1) outline the theoretical importance of implicit processes in patients' self-regulation of illness and methods to study them; (2) review research evidence for these processes, including interventions tested to modify them; and (3) outline avenues for future research. A substantial body of research on implicit processes (cognitive bias and interpretational bias) in illness maintenance in chronic illness has recently been extended to detection and interpretation of acute illness and new perspectives relating to the self-system. There is encouraging evidence that cognitive accessibility of coping and implicit attitudes may impact upon coping behaviours. Procedures that strategically automatise coping responses and create habits have considerable promise. We outline an agenda for future research in which health psychology accepts the challenge posed by the interplay of the reflective and associative systems in promoting effective self-regulation of illness.
Topics: Adaptation, Psychological; Attention; Behavioral Medicine; Chronic Disease; Cognition; Cues; Diagnostic Self Evaluation; Disease; Humans; Models, Psychological; Self-Control
PubMed: 30033853
DOI: 10.1080/17437199.2018.1503559