-
Medicina (Kaunas, Lithuania) Nov 2023Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology with limited treatment options. The role of the immune system in IPF has received... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology with limited treatment options. The role of the immune system in IPF has received increasing attention. Uncontrolled immune responses drive the onset and progression of IPF. This article provides an overview of the role of innate immune cells (including macrophages, neutrophils, mast cells, eosinophils, dendritic cells, nature killer cells, nature kill cells and γδ T cells) and adaptive immune cells (including Th1 cells, Th2 cells, Th9 cells, Th17 cells, Th22 cells, cytotoxic T cells, B lymphocytes and Treg cells) in IPF. In addition, we review the current status of pharmacological treatments for IPF and new developments in immunotherapy. A deeper comprehension of the immune system's function in IPF may contribute to the development of targeted immunomodulatory therapies that can alter the course of the disease.
Topics: Humans; Idiopathic Pulmonary Fibrosis; T-Lymphocytes, Regulatory; Macrophages; Neutrophils; Mast Cells
PubMed: 38004032
DOI: 10.3390/medicina59111984 -
Biosensors & Bioelectronics Jul 2023As a full-fidelity simulation of human cells, tissues, organs, and even systems at the microscopic scale, Organ-on-a-Chip (OOC) has significant ethical advantages and... (Review)
Review
As a full-fidelity simulation of human cells, tissues, organs, and even systems at the microscopic scale, Organ-on-a-Chip (OOC) has significant ethical advantages and development potential compared to animal experiments. The need for the design of new drug high-throughput screening platforms and the mechanistic study of human tissues/organs under pathological conditions, the evolving advances in 3D cell biology and engineering, etc., have promoted the updating of technologies in this field, such as the iteration of chip materials and 3D printing, which in turn facilitate the connection of complex multi-organs-on-chips for simulation and the further development of technology-composite new drug high-throughput screening platforms. As the most critical part of organ-on-a-chip design and practical application, verifying the success of organ model modeling, i.e., evaluating various biochemical and physical parameters in OOC devices, is crucial. Therefore, this paper provides a logical and comprehensive review and discussion of the advances in organ-on-a-chip detection and evaluation technologies from a broad perspective, covering the directions of tissue engineering scaffolds, microenvironment, single/multi-organ function, and stimulus-based evaluation, and provides a more comprehensive review of the progress in the significant organ-on-a-chip research areas in the physiological state.
Topics: Animals; Humans; Microphysiological Systems; Biosensing Techniques; Organoids; Tissue Engineering; Microfluidics; Lab-On-A-Chip Devices
PubMed: 37058958
DOI: 10.1016/j.bios.2023.115285 -
Frontiers in Pharmacology 2024Protein glycosylation is an extensively studied field, with the most studied forms being oxygen or nitrogen-linked N-acetylglucosamine (O-GlcNAc or N-GlcNAc)... (Review)
Review
Protein glycosylation is an extensively studied field, with the most studied forms being oxygen or nitrogen-linked N-acetylglucosamine (O-GlcNAc or N-GlcNAc) glycosylation. Particular residues on proteins are targeted by O-GlcNAcylation, which is among the most intricate post-translational modifications. Significantly contributing to an organism's proteome, it influences numerous factors affecting protein stability, function, and subcellular localization. It also modifies the cellular function of target proteins that have crucial responsibilities in controlling pathways related to the central nervous system, cardiovascular homeostasis, and other organ functions. Under conditions of acute stress, changes in the levels of O-GlcNAcylation of these proteins may have a defensive function. Nevertheless, deviant O-GlcNAcylation nullifies this safeguard and stimulates the advancement of several ailments, the prognosis of which relies on the cellular milieu. Hence, this review provides a concise overview of the function and comprehension of O-GlcNAcylation in ischemia diseases, aiming to facilitate the discovery of new therapeutic targets for efficient treatment, particularly in patients with diabetes.
PubMed: 38783961
DOI: 10.3389/fphar.2024.1377235 -
Cellular Signalling Jan 2024The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its... (Review)
Review
The immune system assumes a pivotal role in the organism's capacity to discern and obliterate malignant cells. The immunogenicity of a cancer cell pertains to its proficiency in inciting an immunological response. The prowess of immunogenicity stands as a pivotal determinant in the triumph of formulating immunotherapeutic methodologies. Immunotherapeutic strategies include immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and on vaccines. Immunogenic cell death (ICD) epitomizes a form of cellular demise that incites an immune response against dying cells. ICD is characterized by the liberation of distinct specific molecules that activate the immune system, thereby leading to the identification and elimination of dying cells by immunocytes. One of the salient characteristics inherent to the ICD phenomenon resides in the vigorous liberation of adenosine triphosphate (ATP) by cellular entities dedicated to embarking upon the process of programmed cell death, yet refraining from complete apoptotic demise. ICD is initiated by a sequence of molecular events that occur during cell death. These occurrences encompass the unveiling or discharge of molecules such as calreticulin, high-mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) from dying cells. These molecules act as "eat me" signals, which are recognized by immune cells, thereby prompting the engulfment and deterioration of expiring cells by phagocytes including various pathways such as Necroptosis, Apoptosis, and pyroptosis. Here, we review our current understanding of the pathophysiological importance of the immune responses against dying cells and the mechanisms underlying their activation. Overall, the ICD represents an important mechanism by which the immune system recognizes and eliminates dying cells, including cancer cells. Understanding the molecular events that underlie ICD bears the potential to engender innovative cancer therapeutics that harness the power of the immune system to combat cancer.
Topics: Humans; Cell Death; Apoptosis; Neoplasms; Pyroptosis; Adenosine Triphosphate
PubMed: 38084844
DOI: 10.1016/j.cellsig.2023.110952 -
JHEP Reports : Innovation in Hepatology Sep 2023Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterised by the presence of one or more organ failures,... (Review)
Review
Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterised by the presence of one or more organ failures, intense systemic inflammation, peripheral blood lymphopenia, and a high risk of death without liver transplantation within 28 days. Herein, we propose the hypothesis that intense systemic inflammation may lead to organ failures through five different non-mutually exclusive mechanisms. First, pathogen-associated molecular patterns and inflammatory mediators ( cytokines and lipid mediators) stimulate the production of the vasorelaxant nitric oxide in the walls of splanchnic arterioles, leading to enhanced splanchnic and systemic vasodilation which, in turn, induces enhanced activity of endogenous vasoconstrictor systems causing renal vasoconstriction and acute kidney injury. Second, neutrophils that reach the systemic circulation are prone to adhere to the vascular endothelium. Cytokines and lipid mediators act on the endothelium in microvessels of vital organs, an effect that favours the migration of neutrophils (and probably other leukocytes) to surrounding tissues where neutrophils can cause tissue damage and thereby contribute to organ failure. Third, cytokines and lipid mediators promote the formation of microthrombi that impair microcirculation and tissue oxygenation. Fourth, acute inflammation stimulates intense peripheral catabolism of amino acids whose products may be metabotoxins that contribute to hepatic encephalopathy. Fifth, acute inflammatory responses, which include the production of a broad variety of biomolecules (proteins and lipids), and an increase in biomass (., granulopoiesis requiring nucleotide synthesis), among others, are energetically expensive processes that require large amounts of nutrients. Therefore, immunity competes with other maintenance programmes for energy. The brain stem integrates the energy demand of each organ system, with immunity considered a top priority. The brain stem may "decide" to make a trade-off which involves the induction of a dormancy programme that permits the shutdown of mitochondrial respiration and oxidative phosphorylation in peripheral organs. In the context of acutely decompensated cirrhosis, the consequence of a shutdown of mitochondrial respiration and ATP production would be a dramatic decrease in organ function.
PubMed: 37600957
DOI: 10.1016/j.jhepr.2023.100807 -
Nature Reviews. Nephrology Feb 2024The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of... (Review)
Review
The homeostasis and health of an organism depend on the coordinated interaction of specialized organs, which is regulated by interorgan communication networks of circulating soluble molecules and neuronal connections. Many diseases that seemingly affect one primary organ are really multiorgan diseases, with substantial secondary remote organ complications that underlie a large part of their morbidity and mortality. Acute kidney injury (AKI) frequently occurs in critically ill patients with multiorgan failure and is associated with high mortality, particularly when it occurs together with respiratory failure. Inflammatory lung lesions in patients with kidney failure that could be distinguished from pulmonary oedema due to volume overload were first reported in the 1930s, but have been largely overlooked in clinical settings. A series of studies over the past two decades have elucidated acute and chronic kidney-lung and lung-kidney interorgan communication networks involving various circulating inflammatory cytokines and chemokines, metabolites, uraemic toxins, immune cells and neuro-immune pathways. Further investigations are warranted to understand these clinical entities of high morbidity and mortality, and to develop effective treatments.
Topics: Humans; Kidney; Lung; Acute Kidney Injury; Respiratory Insufficiency; Cytokines; Critical Illness
PubMed: 37667081
DOI: 10.1038/s41581-023-00760-7 -
Frontiers in Aging 2023Aging is accompanied by a dysregulation of adaptive processes. On the one hand, physiological adaptation mechanisms such as learning and memory, immune system plasticity...
Aging is accompanied by a dysregulation of adaptive processes. On the one hand, physiological adaptation mechanisms such as learning and memory, immune system plasticity and exercise-dependent muscle remodeling are blunted. On the other hand, several maladaptive processes increase with age including cancer, pathological cardiovascular remodeling and metabolic dysregulation. With increasing age the quotient of beneficial adaptation (Ab) to harmful adaptation (Ah), Ab/Ah, decreases. The adaptation-maladaptation framework of aging entails that there are age-related pathological phenotypes that are the result of activation of physiological adaptation mechanisms (e.g., maladaptation as a result of misdirection of adaptive cascades and molecular damage incurred by adaptation processes) and their occurrence over time might, to some degree, be inevitable. Aging might hence result from the organism's inability to solve the adaptation-maladaptation dilemma. The present work explores the concept of counteracting aging through adaptation and proposes that interventions such as exercise, environmental enrichment and dietary restriction work in counteracting aging because they increase the ratio Ab/Ah by both raising Ab (e.g., by inducing metaplasticity in cells, meaning they raise the adaptability of cells to future stimuli) and decreasing Ah (e.g., through desensitizing certain potentially harmful adaptive mechanisms). Molecules whose aging-related expression changes can explain aspects of dysfunctional adaptation such as CREB and certain immediate early genes are examined and it is delineated how a better understanding of the dynamical organization of adaptation cascades could elucidate the seemingly complex role of adaptation in driving aging as well as protecting against it.
PubMed: 37701757
DOI: 10.3389/fragi.2023.1256844 -
Journal of Alzheimer's Disease : JAD 2024Aging is an intrinsic aspect of an organism's life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many... (Review)
Review
Aging is an intrinsic aspect of an organism's life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many age-associated disorders, including neurological disorders, are most commonly linked with the aging process, such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the effects of aging and AD on the molecular pathways and levels of different proteins in the brain, including metalloproteins, neurotrophic factors, amyloid proteins, and tau proteins. AD is caused by the aggregation of amyloid proteins in the brain. Factors such as metal ions, protein ligands, and the oligomerization state of amyloid precursor protein significantly influence the proteolytic processing of amyloid-β protein precursor (AβPP). Tau, a disordered cytosolic protein, serves as the principal microtubule-associated protein in mature neurons. AD patients exhibit decreased levels of nerve growth factor within their nervous systems and cerebrospinal fluid. Furthermore, a significant increase in brain-derived neurotrophic factor resulting from the neuroprotective effect of glial cell line-derived neurotrophic factor suggests that the synergistic action of these proteins plays a role in inhibiting neuronal degeneration and atrophy. The mechanism through which Aβ and AβPP govern Cu2+ transport and their influence on Cu2+ and other metal ion pools requires elucidation in future studies. A comprehensive understanding of the influence of aging and AD on molecular pathways and varying protein levels may hold the potential for the development of novel diagnostic and therapeutic methods for the treatment of AD.
Topics: Humans; Aging; Brain; Alzheimer Disease; Animals; tau Proteins
PubMed: 38339930
DOI: 10.3233/JAD-230801 -
Biometals : An International Journal on... Jun 2024Cadmium (Cd) is an important environmental pollutant that poses a threat to human health and represents a critical component of air pollutants, food sources, and... (Review)
Review
Cadmium (Cd) is an important environmental pollutant that poses a threat to human health and represents a critical component of air pollutants, food sources, and cigarette smoke. Cd is a known carcinogen and has toxic effects on the environment and various organs in humans. Heavy metals within an organism are difficult to biodegrade, and those that enter the respiratory tract are difficult to remove. Autophagy is a key mechanism for counteracting extracellular (microorganisms and foreign bodies) or intracellular (damaged organelles and proteins that cannot be degraded by the proteasome) stress and represents a self-protective mechanism for eukaryotes against heavy metal toxicity. Autophagy maintains cellular homeostasis by isolating and gathering information about foreign chemicals associated with other molecular events. However, autophagy may trigger cell death under certain pathological conditions, including cancer. Autophagy dysfunction is one of the main mechanisms underlying Cd-induced cytotoxicity. In this review, the toxic effects of Cd-induced autophagy on different human organ systems were evaluated, with a focus on hepatotoxicity, nephrotoxicity, respiratory toxicity, and neurotoxicity. This review also highlighted the classical molecular pathways of Cd-induced autophagy, including the ROS-dependent signaling pathways, endoplasmic reticulum (ER) stress pathway, Mammalian target of rapamycin (mTOR) pathway, Beclin-1 and Bcl-2 family, and recently identified molecules associated with Cd. Moreover, research directions for Cd toxicity regarding autophagic function were proposed. This review presents the latest theories to comprehensively reveal autophagy behavior in response to Cd toxicity and proposes novel potential autophagy-targeted prevention and treatment strategies for Cd toxicity and Cd-associated diseases in humans.
Topics: Autophagy; Humans; Cadmium; Animals; Endoplasmic Reticulum Stress; Signal Transduction; Environmental Pollutants
PubMed: 38277035
DOI: 10.1007/s10534-023-00581-y -
Journal of Fungi (Basel, Switzerland) Mar 2024This review explores the 'gut-lung axis' in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community... (Review)
Review
This review explores the 'gut-lung axis' in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community composition alter lung immune function. We comprehensively review available studies that have profiled the composition of the gut mycobiome in adults and children with asthma, and discuss mechanisms of gut-lung interactions that have been described in animal models of asthma. Studies indicate that intestinal fungal dysbiosis, such as an increased abundance of certain fungi like , can elevate the risk of asthma in children and exacerbate it in adults. This effect is mediated through various pathways: the host immune system's sensing of dysbiosis via C-type lectin receptors (e.g., Dectin-2), the impact of pro-inflammatory fungal metabolites (e.g., 12,13-diHOME, prostaglandin E2), and the role of lung immune cells (e.g., group 2 innate lymphoid cells [ILC2], M2 macrophages). We also describe strategies for modulating the gut mycobiome as potential therapies for severe asthma. The review concludes by emphasizing the necessity for further research into the role of the gut mycobiome in asthma to deepen our understanding of these complex interactions.
PubMed: 38535201
DOI: 10.3390/jof10030192