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International Journal of Molecular... Mar 2022The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligand... (Review)
Review
The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligand (ephrins). Its significance in a wide variety of physiologic and pathologic processes has been recognized during the past decades. In carcinogenesis, EPH/ephrins coordinate a wide spectrum of pathologic processes, such as angiogenesis, vessel infiltration, and metastasis. Despite the recent advances in colorectal cancer (CRC) diagnosis and treatment, it remains a leading cause of death globally, accounting for 9.2% of all cancer deaths. A growing body of literature has been published lately revitalizing our scientific interest towards the role of EPH/ephrins in pathogenesis and the treatment of CRC. The aim of the present review is to present the recent CRC data which might lead to clinical practice changes in the future.
Topics: Colorectal Neoplasms; Ephrins; Humans; Neovascularization, Pathologic; Receptors, Eph Family; Signal Transduction
PubMed: 35269901
DOI: 10.3390/ijms23052761 -
Radiology Mar 2021The increasing prevalence of dementia worldwide places a high demand on healthcare providers to perform a diagnostic work-up in relatively early stages of the disease,... (Review)
Review
The increasing prevalence of dementia worldwide places a high demand on healthcare providers to perform a diagnostic work-up in relatively early stages of the disease, given that the pathologic process usually begins decades before symptoms are evident. Structural imaging is recommended to rule out other disorders and can only provide diagnosis in a late stage with limited specificity. Where PET imaging previously focused on the spatial pattern of hypometabolism, the past decade has seen the development of novel tracers to demonstrate characteristic protein abnormalities. Molecular imaging using PET/SPECT is able to show amyloid and tau deposition in Alzheimer disease and dopamine depletion in parkinsonian disorders starting decades before symptom onset. Novel tracers for neuroinflammation and synaptic density are being developed to further unravel the molecular pathologic characteristics of dementia disorders. In this article, the authors review the current status of established and emerging PET tracers in a diagnostic setting and also their value as prognostic markers in research studies and outcome measures for clinical trials in Alzheimer disease.
Topics: Dementia; Disease Progression; Early Diagnosis; Humans; Molecular Imaging; Neuroimaging; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon
PubMed: 33464184
DOI: 10.1148/radiol.2020200028 -
International Journal of Ophthalmology 2019The prevalence of eye diseases worldwide is dramatically increasing and represents a major concern in underdeveloped and developed regions. Ocular diseases, previously... (Review)
Review
The prevalence of eye diseases worldwide is dramatically increasing and represents a major concern in underdeveloped and developed regions. Ocular diseases, previously associated with a higher depression risk, also impose a substantial economic burden on affected families, thus early detection and/or accurate treatment in order to avoid and prevent blindness should be emphasized. Ocular neovascularization (NV), the leading cause of blindness in a variety of eye diseases, is a pathologic process characterized by the formation, proliferation and infiltration of anomalous, tiny and leaky fragile blood vessels within the eye. Genetics have been suspected to play an important role in the occurrence of eye diseases, with the detection of a numbers of specific gene mutations. Long non-coding RNA (lncRNAs) are novel class of regulatory molecules previously associated with various biological processes and diseases, however the nature of the relation and pathways by which they might contribute to the development of corneal, choroidal and retinal NV have not yet been completely elucidated. In this review, we focus on the regulation and characteristics of lncRNAs, summarize results from ocular NV-related studies and discuss the implication of lncRNAs in ocular NV development.
PubMed: 31850182
DOI: 10.18240/ijo.2019.12.19 -
Biomedicine & Pharmacotherapy =... Mar 2022Tumour-derived exosomes (TDEs) are actively produced and released by tumour cells and carry messages from tumour cells to normal or abnormal cells residing at close or... (Review)
Review
Tumour-derived exosomes (TDEs) are actively produced and released by tumour cells and carry messages from tumour cells to normal or abnormal cells residing at close or distant sites. TDEs participate in every process of tumour metastasis. However, the occurrence and development of tumours depend on the specific functions acquired by tumour cells on the primary and metastatic foci. In this review, we discussed that TDEs regulate the initial mechanism of metastasis, the formation of a pre-metastatic niche, immunosuppression and angiogenesis. In addition, we investigated the signalling pathways and effective components of TDEs and discussed that inhibition of exosomes can inhibit tumour progression. Finally, we discussed the application and future development of TDEs. An understanding of several molecular players and processes involved in metastasis can lead to the development of effective, targeted approaches to prevent metastasis and treat cancer.
Topics: Epithelial-Mesenchymal Transition; Exosomes; Extracellular Matrix; Hippo Signaling Pathway; Humans; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Tumor Microenvironment
PubMed: 35078096
DOI: 10.1016/j.biopha.2022.112657 -
International Journal of Molecular... Feb 2019As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic... (Review)
Review
As part of the blood-brain-barrier, astrocytes are ideally positioned between cerebral vasculature and neuronal synapses to mediate nutrient uptake from the systemic circulation. In addition, astrocytes have a robust enzymatic capacity of glycolysis, glycogenesis and lipid metabolism, managing nutrient support in the brain parenchyma for neuronal consumption. Here, we review the plasticity of astrocyte energy metabolism under physiologic and pathologic conditions, highlighting age-dependent brain dysfunctions. In astrocytes, glycolysis and glycogenesis are regulated by noradrenaline and insulin, respectively, while mitochondrial ATP production and fatty acid oxidation are influenced by the thyroid hormone. These regulations are essential for maintaining normal brain activities, and impairments of these processes may lead to neurodegeneration and cognitive decline. Metabolic plasticity is also associated with (re)activation of astrocytes, a process associated with pathologic events. It is likely that the recently described neurodegenerative and neuroprotective subpopulations of reactive astrocytes metabolize distinct energy substrates, and that this preference is supposed to explain some of their impacts on pathologic processes. Importantly, physiologic and pathologic properties of astrocytic metabolic plasticity bear translational potential in defining new potential diagnostic biomarkers and novel therapeutic targets to mitigate neurodegeneration and age-related brain dysfunctions.
Topics: Adaptation, Physiological; Aging; Animals; Astrocytes; Brain; Energy Metabolism; Humans
PubMed: 30795555
DOI: 10.3390/ijms20040941 -
Journal of Immunology (Baltimore, Md. :... Nov 2020Regulatory T cells (Tregs) are crucial mediators of immune homeostasis. They regulate immune response by suppressing inflammation and promoting self-tolerance. In... (Review)
Review
Regulatory T cells (Tregs) are crucial mediators of immune homeostasis. They regulate immune response by suppressing inflammation and promoting self-tolerance. In addition to their immunoregulatory role, a growing body of evidence highlights the dynamic role of Tregs in angiogenesis, the process of forming new blood vessels. Although angiogenesis is critically important for normal tissue regeneration, it is also a hallmark of pathological processes, including malignancy and chronic inflammation. Interestingly, the role of Tregs in angiogenesis has been shown to be highly tissue- and context-specific and as a result can yield either pro- or antiangiogenic effects. For these reasons, there is considerable interest in determining the molecular underpinnings of Treg-mediated modulation of angiogenesis in different disease states. The present review summarizes the role of Tregs in angiogenesis and mechanisms by which Tregs regulate angiogenesis and discusses how these mechanisms differ in homeostatic and pathological settings.
Topics: Animals; Humans; Inflammation; Models, Animal; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Signal Transduction; T-Lymphocytes, Regulatory; Vascular Endothelial Growth Factor A
PubMed: 33168598
DOI: 10.4049/jimmunol.2000574 -
Clinics in Geriatric Medicine Nov 2013Knowledge of aging and dementia is rapidly evolving with the aim of identifying individuals in the earliest stages of disease processes. Biomarkers allow clinicians to... (Review)
Review
Knowledge of aging and dementia is rapidly evolving with the aim of identifying individuals in the earliest stages of disease processes. Biomarkers allow clinicians to show the presence of a pathologic process and resultant synapse dysfunction and neurodegeneration, even in the earliest stages. This article focuses on biomarkers for mild cognitive impairment caused by Alzheimer disease, structural magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (PET) or single-photon emission computed tomography, and PET with dopamine ligands. Although these biomarkers are useful, several limitations exist. Several new biomarkers are emerging and a more biological characterization of underlying pathophysiologic spectra may become possible.
Topics: Aged; Amyloid beta-Peptides; Biomarkers; Brain; Cognitive Dysfunction; Humans; Peptide Fragments; tau Proteins
PubMed: 24094298
DOI: 10.1016/j.cger.2013.07.006 -
Cells Feb 2022Angiogenesis is a vital biological process, and neovascularization is essential for the development, wound repair, and perfusion of ischemic tissue. Neovascularization... (Review)
Review
Angiogenesis is a vital biological process, and neovascularization is essential for the development, wound repair, and perfusion of ischemic tissue. Neovascularization and inflammation are independent biological processes that are linked in response to injury and ischemia. While clear that pro-inflammatory factors drive angiogenesis, the role of anti-inflammatory interleukins in angiogenesis remains less defined. An interleukin with anti-inflammatory yet pro-angiogenic effects would hold great promise as a therapeutic modality to treat many disease states where inflammation needs to be limited, but revascularization and reperfusion still need to be supported. As immune modulators, interleukins can polarize macrophages to a pro-angiogenic and reparative phenotype, which indirectly influences angiogenesis. Interleukins could also potentially directly induce angiogenesis by binding and activating its receptor on endothelial cells. Although a great deal of attention is given to the negative effects of pro-inflammatory interleukins, less is described concerning the potential protective effects of anti-inflammatory interleukins on various disease processes. To focus this review, we will consider IL-4, IL-10, IL-13, IL-19, and IL-33 to be anti-inflammatory interleukins, all of which have recognized immunomodulatory effects. This review will summarize current research concerning anti-inflammatory interleukins as potential drivers of direct and indirect angiogenesis, emphasizing their role in future therapeutics.
Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents; Endothelial Cells; Humans; Inflammation; Interleukins; Ischemia; Neovascularization, Pathologic
PubMed: 35159396
DOI: 10.3390/cells11030587 -
Oncogene Sep 2017TGF-β is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the...
TGF-β is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-β signaling are process-and stage-dependent, and it is not uncommon that TGF-β exerts distinct and sometimes opposing effects on a disease progression depending on the stage and on the pathological changes associated with the stage. The mechanisms underlying cell- and process-specific effects of TGF-β are poorly understood. We are describing a novel pathway that mediates induction of angiogenesis in response to TGF-β1. We found that in endothelial cells (EC) thrombospondin-4 (TSP-4), a secreted extracellular matrix (ECM) protein, is upregulated in response to TGF-β1 and mediates the effects of TGF-β1 on angiogenesis. Upregulation of TSP-4 does not require the synthesis of new protein, is not caused by decreased secretion of TSP-4, and is mediated by activation of SMAD3. Using Thbs4 mice and TSP-4 shRNA, we found that TSP-4 mediated pro-angiogenic functions in cultured EC and angiogenesis in vivo in response to TGF-β1. We observed~3-fold increases in tumor mass and levels of angiogenesis markers in animals injected with TGF-β1, and these effects did not occur in Thbs4 animals. Injections of an inhibitor of TGF-β1 signaling SB-431542 also decreased the weights of tumors and cancer angiogenesis. Our results from in vivo angiogenesis models and cultured EC document that TSP-4 mediates upregulation of angiogenesis by TGF-β1. Upregulation of pro-angiogenic TSP-4 and selective effects of TSP-4 on EC may contribute to stimulation of tumor growth by TGF-β despite the inhibition of cancer cell proliferation.
Topics: Angiogenesis Inducing Agents; Animals; Cell Movement; Cell Proliferation; Cells, Cultured; Chick Embryo; Endothelium, Vascular; Female; Gene Expression Regulation; Humans; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Neovascularization, Pathologic; Signal Transduction; Thrombospondins; Transforming Growth Factor beta
PubMed: 28481870
DOI: 10.1038/onc.2017.140