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Frontiers in Immunology 2023Chorioamnionitis, commonly referred to as intrauterine infection or inflammation, is pathologically defined by neutrophil infiltration and inflammation at the... (Review)
Review
Chorioamnionitis, commonly referred to as intrauterine infection or inflammation, is pathologically defined by neutrophil infiltration and inflammation at the maternal-fetal interface. Chorioamnionitis is the common complication during late pregnancy, which lead to a series of serious consequences, such as preterm labor, preterm premature rupture of the fetal membranes, and fetal inflammatory response syndrome. During infection, a large number of neutrophils migrate to the chorio-decidua in response to chemokines. Although neutrophils, a crucial part of innate immune cells, have strong anti-inflammatory properties, over-activating them can harm the body while also eliminating pathogens. This review concentrated on the latest studies on chorioamnionitis-related consequences as well as the function and malfunction of neutrophils. The release of neutrophil extracellular traps, production of reactive oxygen species, and degranulation from neutrophils during intrauterine infection, as well as their pathological roles in complications related to chorioamnionitis, were discussed in detail, offering fresh perspectives on the treatment of chorioamnionitis.
Topics: Female; Infant, Newborn; Pregnancy; Humans; Chorioamnionitis; Neutrophils; Inflammation; Extracellular Traps; Premature Birth
PubMed: 37475854
DOI: 10.3389/fimmu.2023.1198831 -
Neuro-oncology Oct 2022Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need...
BACKGROUND
Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests.
METHODS
We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families.
RESULTS
We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient's disease course.
CONCLUSIONS
We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care.
Topics: Adolescent; Brain Neoplasms; Cell-Free Nucleic Acids; Central Nervous System Neoplasms; Child; Glioma; High-Throughput Nucleotide Sequencing; Humans; Mutation; Pathology, Molecular; Young Adult
PubMed: 35148412
DOI: 10.1093/neuonc/noac035 -
Genes Dec 2022The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune... (Review)
Review
The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially dysfunctional fatty acid (FA) metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.
Topics: Humans; Glycolysis; Neovascularization, Pathologic; Endothelial Cells; Lipid Metabolism; Fatty Acids
PubMed: 36553568
DOI: 10.3390/genes13122301 -
Molecular Medicine Reports Jan 2022Efferocytosis, the phagocytosis of apoptotic cells performed by both specialized phagocytes (such as macrophages) and non‑specialized phagocytes (such as epithelial... (Review)
Review
Efferocytosis, the phagocytosis of apoptotic cells performed by both specialized phagocytes (such as macrophages) and non‑specialized phagocytes (such as epithelial cells), is involved in tissue repair and homeostasis. Effective efferocytosis prevents secondary necrosis, terminates inflammatory responses, promotes self‑tolerance and activates pro‑resolving pathways to maintain homeostasis. When efferocytosis is impaired, apoptotic cells that could not be cleared in time aggregate, resulting in the necrosis of apoptotic cells and release of pro‑inflammatory factors. In addition, defective efferocytosis inhibits the intracellular cholesterol reverse transportation pathways, which may lead to atherosclerosis, lung damage, non‑alcoholic fatty liver disease and neurodegenerative diseases. The uncleared apoptotic cells can also release autoantigens, which can cause autoimmune diseases. Cancer cells escape from phagocytosis via efferocytosis. Therefore, new treatment strategies for diseases related to defective efferocytosis are proposed. This review illustrated the mechanisms of efferocytosis in multisystem diseases and organismal homeostasis and the pathophysiological consequences of defective efferocytosis. Several drugs and treatments available to enhance efferocytosis are also mentioned in the review, serving as new evidence for clinical application.
Topics: Animals; Apoptosis; Cytophagocytosis; Disease; Epithelial Cells; Extracellular Vesicles; Homeostasis; Humans; Immunity; Inflammation; Macrophages; Necrosis; Pathology; Phagocytes
PubMed: 34779503
DOI: 10.3892/mmr.2021.12529 -
Parasitology Jul 2020Helminth parasitology is an important discipline, which poses often unique technical challenges. One challenge is that helminth parasites, particularly those in humans,... (Review)
Review
Helminth parasitology is an important discipline, which poses often unique technical challenges. One challenge is that helminth parasites, particularly those in humans, are often difficult to obtain alive and in sufficient quantities for study; another is the challenge of studying these organisms in vitro - no helminth parasite life cycle has been fully recapitulated outside of a host. Arguably, the key issue retarding progress in helminth parasitology has been a lack of experimental tools and resources, certainly relative to the riches that have driven many parasitologists to adopt free-living model organisms as surrogate systems. In response to these needs, the past 10-12 years have seen the beginnings of helminth parasitology's journey into the 'omics' era, with the release of abundant sequencing resources, and the functional genomics tools with which to test biological hypotheses. To reflect this progress, the 2019 Autumn Symposium of the British Society for Parasitology was held in Queen's University Belfast on the topic of 'post-genomic progress in helminth parasitology'. This issue presents examples of the current state of play in the field, while this editorial summarizes how genomic datasets and functional genomic tools have stimulated impressive recent progress in our understanding of parasite biology.
Topics: Animals; Anthelmintics; CRISPR-Cas Systems; Drug Resistance; Genome, Helminth; Genomics; Helminthiasis; Helminths; Humans; Parasitology; Pathology, Molecular; Proteomics; RNA Interference; Transcriptome
PubMed: 32252832
DOI: 10.1017/S0031182020000591 -
International Journal of Molecular... Sep 2022The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor... (Review)
Review
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. Recent advances have shown that tumor endothelial cell metabolism is reprogrammed, and that targeting endothelial metabolic pathways impacts developmental and pathological vessel sprouting. Therefore, the use of metabolic antiangiogenic therapies to normalize the blood vasculature, in combination with immunotherapies, offers a clinical niche to treat cancer.
Topics: Endothelial Cells; Humans; Immunotherapy; Neoplasms; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 36232355
DOI: 10.3390/ijms231911052 -
Chinese Journal of Traumatology =... Jan 2022Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a... (Review)
Review
Sepsis is a life-threatening clinical syndrome and one of the most challenging health problems in the world. Pathologically, sepsis and septic shock are caused by a dysregulated host immune response to infection, which can eventually lead to multiple organ failure and even death. As an adaptor transporter between the endoplasmic reticulum and Golgi apparatus, stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173) has been found to play a vital role at the intersection of innate immunity, inflammation, autophagy, and cell death in response to invading microbial pathogens or endogenous host damage. There is ample evidence that impaired STING1, through its immune and non-immune functions, is involved in the pathological process of sepsis. In this review, we discuss the regulation and function of the STING1 pathway in sepsis and highlight it as a suitable drug target for the treatment of lethal infection.
Topics: Autophagy; Humans; Immunity, Innate; Multiple Organ Failure; Sepsis; Shock, Septic
PubMed: 34334261
DOI: 10.1016/j.cjtee.2021.07.009 -
Nature Nov 2020Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse...
Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
Topics: Artificial Intelligence; Cell- and Tissue-Based Therapy; Delivery of Health Care; Early Diagnosis; Education, Medical; Europe; Female; Health; Humans; Legislation, Medical; Male; Medicine; Pathology; Single-Cell Analysis
PubMed: 32894860
DOI: 10.1038/s41586-020-2715-9 -
Circulation Research Mar 2023Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally... (Review)
Review
Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally involved in regulating the balance between thrombosis (the terminal event of platelet activation) and hemostasis (a protective response to tissue injury). Although platelets lack the precise cellular control offered by nucleate cells, they are in fact very dynamic cells, enriched in preformed RNA that allows them the capability of de novo protein synthesis which alters the platelet phenotype and responses in physiological and pathological events. Antiplatelet medications have significantly reduced the morbidity and mortality for patients afflicted with thrombotic diseases, including stroke and myocardial infarction. However, it has become apparent in the last few years that platelets play a critical role beyond thrombosis and hemostasis. For example, platelet-derived proteins by constitutive and regulated exocytosis can be found in the plasma and may educate distant tissue including blood vessels. First, platelets are enriched in inflammatory and anti-inflammatory molecules that may regulate vascular remodeling. Second, platelet-derived microparticles released into the circulation can be acquired by vascular endothelial cells through the process of endocytosis. Third, platelets are highly enriched in mitochondria that may contribute to the local reactive oxygen species pool and remodel phospholipids in the plasma membrane of blood vessels. Lastly, platelets are enriched in proteins and phosphoproteins which can be secreted independent of stimulation by surface receptor agonists in conditions of disturbed blood flow. This so-called biomechanical platelet activation occurs in regions of pathologically narrowed (atherosclerotic) or dilated (aneurysmal) vessels. Emerging evidence suggests platelets may regulate the process of angiogenesis and blood flow to tumors as well as education of distant organs for the purposes of allograft health following transplantation. This review will illustrate the potential of platelets to remodel blood vessels in various diseases with a focus on the aforementioned mechanisms.
Topics: Humans; Blood Platelets; Cell-Derived Microparticles; Endothelial Cells; Hemostasis; Platelet Activation; Thrombosis
PubMed: 36927182
DOI: 10.1161/CIRCRESAHA.122.321566