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Cell Feb 2022Adipose tissue, colloquially known as "fat," is an extraordinarily flexible and heterogeneous organ. While historically viewed as a passive site for energy storage, we... (Review)
Review
Adipose tissue, colloquially known as "fat," is an extraordinarily flexible and heterogeneous organ. While historically viewed as a passive site for energy storage, we now appreciate that adipose tissue regulates many aspects of whole-body physiology, including food intake, maintenance of energy levels, insulin sensitivity, body temperature, and immune responses. A crucial property of adipose tissue is its high degree of plasticity. Physiologic stimuli induce dramatic alterations in adipose-tissue metabolism, structure, and phenotype to meet the needs of the organism. Limitations to this plasticity cause diminished or aberrant responses to physiologic cues and drive the progression of cardiometabolic disease along with other pathological consequences of obesity.
Topics: Adaptation, Physiological; Adipocytes, White; Adipose Tissue; Animals; Disease; Health; Humans; Thermogenesis
PubMed: 35120662
DOI: 10.1016/j.cell.2021.12.016 -
Cellular & Molecular Immunology Aug 2020Immunometabolism plays a fundamental role in health and diseases and involves multiple genes and signals. Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is... (Review)
Review
Immunometabolism plays a fundamental role in health and diseases and involves multiple genes and signals. Aconitate decarboxylase 1 (ACOD1; also known as IRG1) is emerging as a regulator of immunometabolism in inflammation and infection. Upregulation of ACOD1 expression occurs in activated immune cells (e.g., macrophages and monocytes) in response to pathogen infection (e.g., bacteria and viruses), pathogen-associated molecular pattern molecules (e.g., LPS), cytokines (e.g., TNF and IFNs), and damage-associated molecular patterns (e.g., monosodium urate). Mechanistically, several immune receptors (e.g., TLRs and IFNAR), adapter proteins (e.g., MYD88), ubiquitin ligases (e.g., A20), and transcription factors (e.g., NF-κB, IRFs, and STATs) form complex signal transduction networks to control ACOD1 expression in a context-dependent manner. Functionally, ACOD1 mediates itaconate production, oxidative stress, and antigen processing and plays dual roles in immunity and diseases. On the one hand, activation of the ACOD1 pathway may limit pathogen infection and promote embryo implantation. On the other hand, abnormal ACOD1 expression can lead to tumor progression, neurodegenerative disease, and immune paralysis. Further understanding of the function and regulation of ACOD1 is important for the application of ACOD1-based therapeutic strategies in disease.
Topics: Animals; Antigen Presentation; Carboxy-Lyases; Disease; Humans; Immune System; Immunity; Oxidative Stress
PubMed: 32601305
DOI: 10.1038/s41423-020-0489-5 -
Seminars in Hematology Jan 2022Bone marrow failure (BMF) syndromes are a heterogeneous group of benign hematological conditions characterized by uni- or multi-lineage marrow and/or peripheral blood... (Review)
Review
Bone marrow failure (BMF) syndromes are a heterogeneous group of benign hematological conditions characterized by uni- or multi-lineage marrow and/or peripheral blood cytopenia(s), and can be classified in constitutional or acquired syndromes based on pathophysiology. In inherited diseases, germline mutations occur in the hematopoietic stem and progenitor cell (HSPC) compartment causing a progressive loss of normal hematopoiesis, while in acquired syndromes, HPSC compartment disruption can be caused by an extrinsic direct damage by external cytotoxic agents on the stem cell pool or by an autoimmune attack against HSPCs. Aplastic anemia is an acquired immune-mediated BMF syndrome where marrow disruption is driven by a cytotoxic T cell-mediated autoimmune attack against HSPCs sustained by type I interferons that polarize the immune system toward T helper 1 responses in early phases and then toward T helper 17 and effector memory CD8 T cell in late stage and severe disease. Cytokines and chemokines also play a crucial role in driving immune responses and HSPC growth inhibition and apoptosis, as described for interferon-γ and tumor necrosis factor α. In this review, we summarize current knowledge on acquired aplastic anemia pathophysiology.
Topics: Anemia, Aplastic; Bone Marrow; Bone Marrow Failure Disorders; Hematopoietic Stem Cells; Humans; Syndrome
PubMed: 35491054
DOI: 10.1053/j.seminhematol.2021.12.002 -
Science (New York, N.Y.) Jan 2020Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the... (Review)
Review
Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The "exposome" concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted.
Topics: Dietary Supplements; Disease; Exposome; Genome, Human; Health; Humans; Organic Chemicals; Physical Phenomena; Risk Assessment; Stress, Psychological
PubMed: 31974245
DOI: 10.1126/science.aay3164 -
The Journal of Allergy and Clinical... Aug 2023Cold urticaria is a chronic condition causing episodic symptoms of cold-induced wheals or angioedema in response to direct or indirect exposure to cold temperatures.... (Review)
Review
Cold urticaria is a chronic condition causing episodic symptoms of cold-induced wheals or angioedema in response to direct or indirect exposure to cold temperatures. Whereas symptoms of cold urticaria are typically benign and self-limiting, severe systemic anaphylactic reactions are possible. Acquired, atypical, and hereditary forms have been described, each with variable triggers, symptoms, and responses to therapy. Clinical testing, including response to cold stimulation, helps define disease subtypes. More recently, monogenic disorders characterized by atypical forms of cold urticaria have been described. Here, we review the different forms of cold-induced urticaria and related syndromes and propose a diagnostic algorithm to aid clinicians in making a timely diagnosis for the appropriate management of these patients.
Topics: Humans; Syndrome; Urticaria; Angioedema; Cold Temperature; Diagnosis, Differential
PubMed: 37290539
DOI: 10.1016/j.jaip.2023.05.040 -
Disease Models & Mechanisms Feb 2020Skeletal muscle fibres are multinucleated cells that contain postmitotic nuclei (i.e. they are no longer able to divide) and perform muscle contraction. They are formed... (Review)
Review
Skeletal muscle fibres are multinucleated cells that contain postmitotic nuclei (i.e. they are no longer able to divide) and perform muscle contraction. They are formed by fusion of muscle precursor cells, and grow into elongating myofibres by the addition of further precursor cells, called satellite cells, which are also responsible for regeneration following injury. Skeletal muscle regeneration occurs in most muscular dystrophies in response to necrosis of muscle fibres. However, the complex environment within dystrophic skeletal muscle, which includes inflammatory cells, fibroblasts and fibro-adipogenic cells, together with the genetic background of the model and the muscle being studied, complicates the interpretation of laboratory studies on muscular dystrophies. Many genes are expressed in satellite cells and in other tissues, which makes it difficult to determine the molecular cause of various types of muscular dystrophies. Here, and in the accompanying poster, we discuss our current knowledge of the cellular mechanisms that govern the growth and regeneration of skeletal muscle, and highlight the defects in satellite cell function that give rise to muscular dystrophies.
Topics: Animals; Disease; Disease Models, Animal; Health; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophies
PubMed: 32066552
DOI: 10.1242/dmm.042192 -
Nature Aug 2021The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile... (Review)
Review
The genomes of virtually all organisms contain repetitive sequences that are generated by the activity of transposable elements (transposons). Transposons are mobile genetic elements that can move from one genomic location to another; in this process, they amplify and increase their presence in genomes, sometimes to very high copy numbers. In this Review we discuss new evidence and ideas that the activity of retrotransposons, a major subgroup of transposons overall, influences and even promotes the process of ageing and age-related diseases in complex metazoan organisms, including humans. Retrotransposons have been coevolving with their host genomes since the dawn of life. This relationship has been largely competitive, and transposons have earned epithets such as 'junk DNA' and 'molecular parasites'. Much of our knowledge of the evolution of retrotransposons reflects their activity in the germline and is evident from genome sequence data. Recent research has provided a wealth of information on the activity of retrotransposons in somatic tissues during an individual lifespan, the molecular mechanisms that underlie this activity, and the manner in which these processes intersect with our own physiology, health and well-being.
Topics: Aging; Animals; DNA Damage; Disease; Gene Silencing; Genome, Human; Genomics; Humans; Immunity, Innate; Retroelements
PubMed: 34349292
DOI: 10.1038/s41586-021-03542-y -
Cellular & Molecular Immunology May 2020Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high... (Review)
Review
Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. Depending on the (patho)physiological context, specific chemoattractant receptors may be up- or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences, thus opening new windows for the identification of disease biomarkers and potential drug targets.
Topics: Animals; Chemotactic Factors; Disease; Health; Humans; Neutrophils; Receptors, Formyl Peptide; Signal Transduction
PubMed: 32238918
DOI: 10.1038/s41423-020-0412-0 -
Biomolecules Sep 2021Pyrroloquinoline quinone (PQQ) is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates... (Review)
Review
Pyrroloquinoline quinone (PQQ) is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates clinically relevant dysfunctions (e.g., those associated with ischemia, inflammation and lipotoxicity). PQQ is novel among biofactors that are not currently accepted as vitamins or conditional vitamins. For example, the absence of PQQ in diets produces a response like a vitamin-related deficiency with recovery upon PQQ repletion in a dose-dependent manner. Moreover, potential health benefits, such as improved metabolic flexibility and immuno-and neuroprotection, are associated with PQQ supplementation. Here, we address PQQ's role as an enzymatic cofactor or accessory factor and highlight mechanisms underlying PQQ's actions. We review both large scale and targeted datasets demonstrating that a neonatal or perinatal PQQ deficiency reduces mitochondria content and mitochondrial-related gene expression. Data are reviewed that suggest PQQ's modulation of lactate acid and perhaps other dehydrogenases enhance NAD+-dependent sirtuin activity, along with the sirtuin targets, such as PGC-1α, NRF-1, NRF-2 and TFAM; thus, mediating mitochondrial functions. Taken together, current observations suggest vitamin-like PQQ has strong potential as a potent therapeutic nutraceutical.
Topics: Animals; Antioxidants; Diet; Disease; Health; Humans; PQQ Cofactor; Vitamins
PubMed: 34680074
DOI: 10.3390/biom11101441 -
Journal of Intensive Care Medicine Dec 2020Multiple organ dysfunction syndrome (MODS) is one of the most common syndromes of critical illness and the leading cause of mortality among critically ill patients....
Multiple organ dysfunction syndrome (MODS) is one of the most common syndromes of critical illness and the leading cause of mortality among critically ill patients. Multiple organ dysfunction syndrome is the clinical consequence of a dysregulated inflammatory response, triggered by clinically diverse factors with the main pillar of management being invasive organ support. During the last years, the advances in the clarification of the molecular pathways that trigger, mitigate, and determine the outcome of MODS have led to the increasing recognition of MODS as a distinct disease entity with distinct etiology, pathophysiology, and potential future therapeutic interventions. Given the lack of effective treatment for MODS, its early recognition, the early intensive care unit admission, and the initiation of invasive organ support remain the most effective strategies of preventing its progression and improving outcomes.
Topics: Critical Illness; Humans; Intensive Care Units; Multiple Organ Failure; Syndrome
PubMed: 31455133
DOI: 10.1177/0885066619871452