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Nature Jun 2023Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate... (Review)
Review
Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate from early yolk sac progenitors and are specified into tissue-specific subsets during organogenesis-establishing stable spatial and functional relationships with specialized tissue cells-and persist in adults. Resident macrophages are an integral part of tissues together with specialized cells: for instance, microglia reside with neurons in brain, osteoclasts reside with osteoblasts in bone, and fat-associated macrophages reside with white adipocytes in adipose tissue. This ancillary cell type, which is developmentally and functionally distinct from haematopoietic stem cell and monocyte-derived macrophages, senses and integrates local and systemic information to provide specialized tissue cells with the growth factors, nutrient recycling and waste removal that are critical for tissue growth, homeostasis and repair. Resident macrophages contribute to organogenesis, promote tissue regeneration following damage and contribute to tissue metabolism and defence against infectious disease. A correlate is that genetic or environment-driven resident macrophage dysfunction is a cause of degenerative, metabolic and possibly inflammatory and tumoural diseases. In this Review, we aim to provide a conceptual outline of our current understanding of macrophage physiology and its importance in human diseases, which may inform and serve the design of future studies.
Topics: Animals; Humans; Cell Differentiation; Cell Lineage; Hematopoietic Stem Cells; Macrophages; Microglia; Monocytes; Organ Specificity; Disease
PubMed: 37344646
DOI: 10.1038/s41586-023-06002-x -
Nature Communications Aug 2018Accumulating evidence implicates metabolites produced by gut microbes as crucial mediators of diet-induced host-microbial cross-talk. Here, we review emerging data... (Review)
Review
Accumulating evidence implicates metabolites produced by gut microbes as crucial mediators of diet-induced host-microbial cross-talk. Here, we review emerging data suggesting that microbial tryptophan catabolites resulting from proteolysis are influencing host health. These metabolites are suggested to activate the immune system through binding to the aryl hydrocarbon receptor (AHR), enhance the intestinal epithelial barrier, stimulate gastrointestinal motility, as well as secretion of gut hormones, exert anti-inflammatory, anti-oxidative or toxic effects in systemic circulation, and putatively modulate gut microbial composition. Tryptophan catabolites thus affect various physiological processes and may contribute to intestinal and systemic homeostasis in health and disease.
Topics: Animals; Bacteria; Digestive System; Disease; Health; Humans; Receptors, Aryl Hydrocarbon; Tryptophan
PubMed: 30120222
DOI: 10.1038/s41467-018-05470-4 -
Zeitschrift Fur Rheumatologie Nov 2022The VEXAS syndrome is a recently identified autoinflammatory systemic disease. The acronym VEXAS stands for Vacuoles, E1 enzyme, X‑linked, Autoinflammatory, Somatic.... (Review)
Review
The VEXAS syndrome is a recently identified autoinflammatory systemic disease. The acronym VEXAS stands for Vacuoles, E1 enzyme, X‑linked, Autoinflammatory, Somatic. The disease is due to an acquired somatic mutation of the UBA1 gene, which encodes for the E‑1 enzyme, which in turn is responsible for the ubiquitination of proteins. Due to its location on the X chromosome, the disease predominantly affects men (in the second half of life). The patients present with a plethora of inflammatory clinical symptoms, often with overlap of hematologic, dermatologic, and rheumatologic syndromes. In particular, the presence of cytoplasmic vacuoles in the bone marrow is characteristic. In this article we report the clinical case of a VEXAS patient and give an overview of the pathophysiology, clinical symptoms and diagnostics of the disease.
Topics: Male; Humans; Syndrome; Mutation
PubMed: 35179640
DOI: 10.1007/s00393-022-01169-6 -
Annual Review of Physiology Feb 2019Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and... (Review)
Review
Phospholipids are major constituents of biological membranes. The fatty acyl chain composition of phospholipids determines the biophysical properties of membranes and thereby affects their impact on biological processes. The composition of fatty acyl chains is also actively regulated through a deacylation and reacylation pathway called Lands' cycle. Recent studies of mouse genetic models have demonstrated that lysophosphatidylcholine acyltransferases (LPCATs), which catalyze the incorporation of fatty acyl chains into the sn-2 site of phosphatidylcholine, play important roles in pathophysiology. Two LPCAT family members, LPCAT1 and LPCAT3, have been particularly well studied. LPCAT1 is crucial for proper lung function due to its role in pulmonary surfactant biosynthesis. LPCAT3 maintains systemic lipid homeostasis by regulating lipid absorption in intestine, lipoprotein secretion, and de novo lipogenesis in liver. Mounting evidence also suggests that changes in LPCAT activity may be potentially involved in pathological conditions, including nonalcoholic fatty liver disease, atherosclerosis, viral infections, and cancer. Pharmacological manipulation of LPCAT activity and membrane phospholipid composition may provide new therapeutic options for these conditions.
Topics: 1-Acylglycerophosphocholine O-Acyltransferase; Animals; Disease; Homeostasis; Humans; Liver; Phospholipids; Signal Transduction
PubMed: 30379616
DOI: 10.1146/annurev-physiol-020518-114444 -
Blood Apr 2011More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each... (Review)
Review
More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.
Topics: Animals; Autoimmune Diseases; Disease; Humans; Inflammation; Interleukin-1; Models, Biological; Molecular Targeted Therapy; Multigene Family; Receptors, Interleukin-1; Toll-Like Receptors
PubMed: 21304099
DOI: 10.1182/blood-2010-07-273417 -
Current Pain and Headache Reports Jan 2022The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last... (Review)
Review
PURPOSE OF REVIEW
The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last few years.
RECENT FINDINGS
Various new triggers and different NDPH mimics have been reported. The association with both cephalic and extracephalic pathologies suggests that NDPH is rather a syndrome with more than one disease mechanism. Recent clinical studies confirmed that migrainous headache remained the most prominent phenotype of NDPH, echoing the change of the diagnostic criteria in 2013. Diagnostic workup, including imaging studies, was unremarkable, except serving to exclude secondary etiologies. Studies on treatment options have yet shown promising targets, and randomized clinical trials are still lacking. Multiple mechanisms, both cranial and systemic, may be involved synergically in the generation of NDPH-like headaches. The search for effective treatment options should base on better understanding of disease mechanisms.
Topics: Headache; Headache Disorders; Humans; Migraine Disorders; Syndrome; Treatment Outcome
PubMed: 35076874
DOI: 10.1007/s11916-022-01005-1 -
Turkish Journal of Medical Sciences Dec 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a disease named as COVID-19, which is composed of multi systemic manifestations with a pulmonary system predominance. As the time passes, we are dealing more and more with a wide variety of effects and complications of the disease in survivors as far as with concerns about the clinical outcome and the timeline of symptoms in different patients. Since the lungs are the most involved organs and the post-COVID prolonged and persistent effects are mainly related to the pulmonary system, it is crucial to define and predict the outcome and to determine the individuals that can progress to fibrosis and loss of function of lungs. This review summarizes the current literature regarding the pulmonary complications in post-COVID syndrome and the management of these conditions.
Topics: COVID-19; Fibrosis; Humans; Lung; Pandemics; SARS-CoV-2; Severe Acute Respiratory Syndrome; Syndrome
PubMed: 34284532
DOI: 10.3906/sag-2106-238 -
Journal of Translational Medicine Jul 2019The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic... (Review)
Review
The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.
Topics: Disease; Gastrointestinal Microbiome; Humans; Lung; Microbiota; Mouth; Smoking
PubMed: 31307469
DOI: 10.1186/s12967-019-1971-7 -
Journal of the American College of... Nov 2008The term cardiorenal syndrome (CRS) increasingly has been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements,... (Review)
Review
The term cardiorenal syndrome (CRS) increasingly has been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of heart-kidney interactions, we present a new classification of the CRS with 5 subtypes that reflect the pathophysiology, the time-frame, and the nature of concomitant cardiac and renal dysfunction. CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. Type 1 CRS reflects an abrupt worsening of cardiac function (e.g., acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS comprises chronic abnormalities in cardiac function (e.g., chronic congestive heart failure) causing progressive chronic kidney disease. Type 3 CRS consists of an abrupt worsening of renal function (e.g., acute kidney ischemia or glomerulonephritis) causing acute cardiac dysfunction (e.g., heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g., chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g., sepsis) causing both cardiac and renal dysfunction. Biomarkers can contribute to an early diagnosis of CRS and to a timely therapeutic intervention. The use of this classification can help physicians characterize groups of patients, provides the rationale for specific management strategies, and allows the design of future clinical trials with more accurate selection and stratification of the population under investigation.
Topics: Acute Disease; Chronic Disease; Disease Progression; Female; Heart Failure; Heart Function Tests; Humans; Kidney Function Tests; Male; Prognosis; Renal Insufficiency; Severity of Illness Index; Syndrome; Terminology as Topic
PubMed: 19007588
DOI: 10.1016/j.jacc.2008.07.051 -
Minerva Anestesiologica May 2010Following successful resuscitation from cardiac arrest, neurological impairment as well as other types of organ dysfunction still cause significant morbidity and... (Review)
Review
Following successful resuscitation from cardiac arrest, neurological impairment as well as other types of organ dysfunction still cause significant morbidity and mortality. The whole-body ischemia-reperfusion response that occurs during cardiac arrest and subsequent restoration of systemic circulation results in a series of pathophysiological processes that have been termed the post-cardiac arrest syndrome. The components of the post-cardiac arrest syndrome comprise post-cardiac arrest brain injury, post-cardiac arrest myocardial dysfunction, the systemic ischemia-reperfusion response and persistent precipitating pathology. Management of the post-cardiac arrest syndrome involves intensive care support with input from various other medical specialties in a coordinated fashion. Management of ventilation aims for normal carbon dioxide values and normoxia rather than hyperoxia. Management of the circulation commonly requires vasoactive support to overcome (often transient) myocardial dysfunction. Particular attention should be given to evidence of cardiac ischemia and referral for urgent angiography and percutaneous coronary intervention, if appropriate, should be available to all. Optimizing neurological recovery will involve seizure control, management of hyperglycemia and therapeutic hypothermia. Prognostication following cardiac arrest remains difficult, but there are diagnostic tests that may be used with some degree of accuracy.
Topics: Heart Arrest; Humans; Nervous System Diseases; Recovery of Function; Reperfusion Injury; Resuscitation; Syndrome
PubMed: 20395899
DOI: No ID Found