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Journal of Lipid Research Apr 2009The prostanoids are a family of lipid mediators generated by the action of cyclooxygenase on a 20-carbon unsaturated fatty acid, arachidonic acid. Prostanoids are... (Review)
Review
The prostanoids are a family of lipid mediators generated by the action of cyclooxygenase on a 20-carbon unsaturated fatty acid, arachidonic acid. Prostanoids are generated widely in response to diverse stimuli and, acting in a paracrine or autocrine manner, play important roles in normal physiology and disease. This review summarizes the current knowledge on prostanoid generation and the roles of individual mediators, their biosynthetic pathways, and their receptors in health and disease.
Topics: Animals; Disease; Health; Humans; Prostaglandins; Receptors, Prostaglandin
PubMed: 19095631
DOI: 10.1194/jlr.R800094-JLR200 -
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 -
Trends in Cell Biology Mar 2017Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound carriers with complex cargoes including proteins, lipids, and nucleic acids. While the... (Review)
Review
Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound carriers with complex cargoes including proteins, lipids, and nucleic acids. While the release of EVs was previously thought to be only a mechanism to discard nonfunctional cellular components, increasing evidence implicates EVs as key players in intercellular and even interorganismal communication. EVs confer stability and can direct their cargoes to specific cell types. EV cargoes also appear to act in a combinatorial manner to communicate directives to other cells. This review focuses on recent findings and knowledge gaps in the area of EV biogenesis, release, and uptake. In addition, we highlight examples whereby EV cargoes control basic cellular functions, including motility and polarization, immune responses, and development, and contribute to diseases such as cancer and neurodegeneration.
Topics: Biological Transport; Disease; Extracellular Space; Extracellular Vesicles; Humans; Membrane Fusion; Models, Biological
PubMed: 27979573
DOI: 10.1016/j.tcb.2016.11.003 -
Experimental Hematology Jul 2010Fibrocytes are circulating mesenchymal progenitor cells that participate in tissue responses to injury and invasion. Accumulating knowledge from animal models regarding... (Review)
Review
Fibrocytes are circulating mesenchymal progenitor cells that participate in tissue responses to injury and invasion. Accumulating knowledge from animal models regarding the differentiation, trafficking, and function of these cells implicates them in the development of diseases characterized by chronic inflammation and excessive collagen deposition. Recent data obtained from the clinical setting suggests that the enumeration of circulating fibrocytes may be a biomarker for disease progression in chronic lung diseases including asthma and pulmonary fibrosis. A greater understanding of the immunologic mediators that influence fibrocyte biology suggests new opportunities for therapeutic manipulation of these cells in fibrogenesis. This review integrates new developments in the cellular and molecular biology of fibrocytes with current concepts regarding the etiopathogenesis of fibrosing disorders.
Topics: Animals; Cell Differentiation; Disease; Fibrosis; Humans; Mesenchymal Stem Cells
PubMed: 20303382
DOI: 10.1016/j.exphem.2010.03.004 -
Experimental Cell Research Nov 2014DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various... (Review)
Review
DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field.
Topics: Animals; DNA Damage; DNA Replication; Disease; Genomic Instability; Humans
PubMed: 25281304
DOI: 10.1016/j.yexcr.2014.09.030 -
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 -
Cellular and Molecular Life Sciences :... Jan 2017The vasculature is one of the most dynamic tissues that encounter numerous mechanical cues derived from pulsatile blood flow, blood pressure, activity of smooth muscle... (Review)
Review
The vasculature is one of the most dynamic tissues that encounter numerous mechanical cues derived from pulsatile blood flow, blood pressure, activity of smooth muscle cells in the vessel wall, and transmigration of immune cells. The inner layer of blood and lymphatic vessels is covered by the endothelium, a monolayer of cells which separates blood from tissue, an important function that it fulfills even under the dynamic circumstances of the vascular microenvironment. In addition, remodeling of the endothelial barrier during angiogenesis and trafficking of immune cells is achieved by specific modulation of cell-cell adhesion structures between the endothelial cells. In recent years, there have been many new discoveries in the field of cellular mechanotransduction which controls the formation and destabilization of the vascular barrier. Force-induced adaptation at endothelial cell-cell adhesion structures is a crucial node in these processes that challenge the vascular barrier. One of the key examples of a force-induced molecular event is the recruitment of vinculin to the VE-cadherin complex upon pulling forces at cell-cell junctions. Here, we highlight recent advances in the current understanding of mechanotransduction responses at, and derived from, endothelial cell-cell junctions. We further discuss their importance for vascular barrier function and remodeling in development, inflammation, and vascular disease.
Topics: Disease; Endothelial Cells; Humans; Intercellular Junctions; Mechanotransduction, Cellular; Neovascularization, Physiologic; Vascular Stiffness
PubMed: 27506620
DOI: 10.1007/s00018-016-2325-8 -
Human Molecular Genetics Oct 2011Over the past 18 months, there have been notable developments in the direct-to-consumer (DTC) genomic testing arena, in particular with regard to issues surrounding... (Review)
Review
Over the past 18 months, there have been notable developments in the direct-to-consumer (DTC) genomic testing arena, in particular with regard to issues surrounding governmental regulation in the USA. While commentaries continue to proliferate on this topic, actual empirical research remains relatively scant. In terms of DTC genomic testing for disease susceptibility, most of the research has centered on uptake, perceptions and attitudes toward testing among health care professionals and consumers. Only a few available studies have examined actual behavioral response among consumers, and we are not aware of any studies that have examined response to DTC genetic testing for ancestry or for drug response. We propose that further research in this area is desperately needed, despite challenges in designing appropriate studies given the rapid pace at which the field is evolving. Ultimately, DTC genomic testing for common markers and conditions is only a precursor to the eventual cost-effectiveness and wide availability of whole genome sequencing of individuals, although it remains unclear whether DTC genomic information will still be attainable. Either way, however, current knowledge needs to be extended and enhanced with respect to the delivery, impact and use of increasingly accurate and comprehensive individualized genomic data.
Topics: Consumer Behavior; Disease; Genetic Testing; Genomics; Humans; Precision Medicine; United States
PubMed: 21828075
DOI: 10.1093/hmg/ddr349 -
Nutrients Jul 2021Alcohol use has been causally linked to more than 200 disease and injury conditions, as defined by three-digit ICD-10 codes. The understanding of how alcohol use is... (Meta-Analysis)
Meta-Analysis Review
Alcohol use has been causally linked to more than 200 disease and injury conditions, as defined by three-digit ICD-10 codes. The understanding of how alcohol use is related to these conditions is essential to public health and policy research. Accordingly, this study presents a narrative review of different dose-response relationships for alcohol use. Relative-risk (RR) functions were obtained from various comparative risk assessments. Two main dimensions of alcohol consumption are used to assess disease and injury risk: (1) volume of consumption, and (2) patterns of drinking, operationalized via frequency of heavy drinking occasions. Lifetime abstention was used as the reference group. Most dose-response relationships between alcohol and outcomes are monotonic, but for diabetes type 2 and ischemic diseases, there are indications of a curvilinear relationship, where light to moderate drinking is associated with lower risk compared with not drinking (i.e., RR < 1). In general, women experience a greater increase in RR per gram of alcohol consumed than men. The RR per gram of alcohol consumed was lower for people of older ages. RRs indicated that alcohol use may interact synergistically with other risk factors, in particular with socioeconomic status and other behavioural risk factors, such as smoking, obesity, or physical inactivity. The literature on the impact of genetic constitution on dose-response curves is underdeveloped, but certain genetic variants are linked to an increased RR per gram of alcohol consumed for some diseases. When developing alcohol policy measures, including low-risk drinking guidelines, dose-response relationships must be taken into consideration.
Topics: Age Factors; Alcohol Drinking; Causality; Disease; Dose-Response Relationship, Drug; Humans; Mortality; Risk Assessment; Risk Factors; Sex Factors; Smoking
PubMed: 34444809
DOI: 10.3390/nu13082652 -
Cells Jun 2023Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional... (Review)
Review
Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is one of the most prevalent neuropsychiatric features of Parkinson's disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.
Topics: Humans; Apathy; Parkinson Disease; Depression; Limbic System; Syndrome; Dihydroxyphenylalanine
PubMed: 37371068
DOI: 10.3390/cells12121599