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Connective Tissue Research May 2023The formyl peptide receptor (FPR) participates in the immune response, with roles in infection and inflammation. In this review article, we summarize the current... (Review)
Review
PURPOSE/AIM OF THE STUDY
The formyl peptide receptor (FPR) participates in the immune response, with roles in infection and inflammation. In this review article, we summarize the current literature on these roles before discussing the function of FPRs in the pathogenesis of musculoskeletal disorders including osteoarthritis (OA), degenerative disc disease (DDD), and rheumatoid arthritis (RA). Additionally, we discuss the potential diagnostic and therapeutic roles of FPRs in these domains.
METHODS
PubMed and Ovid MEDLINE searches were performed from 1965 through March 2022. Keywords included "FPR, tissue expression, inflammation, infection, musculoskeletal disorder, bone, rheumatoid arthritis, osteoarthritis, degenerative disc disease, mitochondria."
RESULTS
Sixty-nine studies were included in this review article. FPRs appear to be ubiquitous in the pathogenesis, diagnosis, and treatment of common musculoskeletal disorders. They can potentially be utilized for the earlier diagnosis of OA and DDD. They may be employed with mesenchymal stem cells (MSCs) to reverse OA and DDD pathologies. With anti-inflammatory, anti-osteolytic, and pro-angiogenic functions, they may broaden treatment options in RA.
CONCLUSIONS
FPRs appear to be heavily involved in the pathogenesis of common musculoskeletal conditions, including arthritis, degenerative disc disease, and rheumatoid arthritis. Furthermore, they demonstrate much promise in the diagnosis and treatment of these conditions. Their roles should continue to be explored.
Topics: Humans; Intervertebral Disc Degeneration; Receptors, Formyl Peptide; Inflammation; Arthritis, Rheumatoid; Osteoarthritis; Musculoskeletal Diseases
PubMed: 36440821
DOI: 10.1080/03008207.2022.2149397 -
Cells Mar 2023Alzheimer's disease (AD) is the most common degenerative disorder in the elderly in developed countries. Currently, growing evidence is pointing at endothelial... (Review)
Review
Alzheimer's disease (AD) is the most common degenerative disorder in the elderly in developed countries. Currently, growing evidence is pointing at endothelial dysfunction as a key player in the cognitive decline course of AD. As a main component of the blood-brain barrier (BBB), the dysfunction of endothelial cells driven by vascular risk factors associated with AD allows the passage of toxic substances to the cerebral parenchyma, producing chronic hypoperfusion that eventually causes an inflammatory and neurotoxic response. In this process, the levels of several biomarkers are disrupted, such as an increase in adhesion molecules that allow the passage of leukocytes to the cerebral parenchyma, increasing the permeability of the BBB; moreover, other vascular players, including endothelin-1, also mediate artery inflammation. As a consequence of the disruption of the BBB, a progressive neuroinflammatory response is produced that, added to the astrogliosis, eventually triggers neuronal degeneration (possibly responsible for cognitive deterioration). Recently, new molecules have been proposed as early biomarkers for endothelial dysfunction that can constitute new therapeutic targets as well as early diagnostic and prognostic markers for AD.
Topics: Humans; Aged; Alzheimer Disease; Endothelial Cells; Blood-Brain Barrier; Cognition Disorders; Vascular Diseases; Biomarkers
PubMed: 36980302
DOI: 10.3390/cells12060962 -
Cerebellum & Ataxias 2019Eye movements are frequently considered diagnostic markers indicating involvement of the cerebellum. Impaired amplitude of saccades (saccade dysmetria), impaired gaze... (Review)
Review
Eye movements are frequently considered diagnostic markers indicating involvement of the cerebellum. Impaired amplitude of saccades (saccade dysmetria), impaired gaze holding function (horizontal or downbeat nystagmus), and interrupted (choppy) pursuit are typically considered hallmarks of cerebellar disorders. While saccade dysmetria is a frequently considered abnormality, the velocity of saccades are rarely considered part of the constellation of cerebellar involvement. Reduced saccade velocity, frequently called "slow saccades" are typically seen in a classic disorder of the midbrain called progressive supranuclear palsy. It is also traditionally diagnostic of spinocerebellar ataxia type 2. In addition to its common causes, the slowness of vertical saccades is not rare in cerebellar disorders. Frequently this phenomenology is seen in multisystem involvement that substantially involves the cerebellum. In this review we will first discuss the physiological basis and the biological need for high saccade velocities. In subsequent sections we will discuss disorders of cerebellum that are known to cause slowing of saccades. We will then discuss possible pathology and novel therapeutic strategies.
PubMed: 30680221
DOI: 10.1186/s40673-018-0095-9 -
The British Journal of Radiology Feb 2017Ankle impingement syndromes encompass a broad spectrum of post-traumatic and chronic degenerative changes that present with pain on specific movements about the ankle... (Review)
Review
Ankle impingement syndromes encompass a broad spectrum of post-traumatic and chronic degenerative changes that present with pain on specific movements about the ankle joint. Both amateur and professional athletes are disproportionately affected by these conditions, and while conservative measures can potentially treat an impingement syndrome, definitive therapy is often alleviated surgically. Imaging (including conventional radiography, ultrasound, CT and MRI) plays an invaluable role in the diagnosis and pre-surgical work-up. An anatomically based classification system is useful in these syndromes, as the aetiology, sites of pathology and preferred treatment methods are similarly based on anatomic locations about the ankle. This review focuses on the anatomic locations, pathophysiology, imaging considerations and brief discussion of therapies for each of the major anatomic ankle impingement syndromes.
Topics: Adult; Ankle Injuries; Ankle Joint; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Range of Motion, Articular; Syndrome; Tomography, X-Ray Computed; Ultrasonography; Young Adult
PubMed: 27885856
DOI: 10.1259/bjr.20160735 -
Neuroscience and Biobehavioral Reviews May 2009Both major depressive disorder and bipolar disorder are the subject of a voluminous imaging and genetics literature. Here, we attempt a comprehensive review of MRI and... (Review)
Review
Both major depressive disorder and bipolar disorder are the subject of a voluminous imaging and genetics literature. Here, we attempt a comprehensive review of MRI and metabolic PET studies conducted to date on these two disorders, and interpret our findings from the perspective of developmental and degenerative models of illness. Elevated activity and volume loss of the hippocampus, orbital and ventral prefrontal cortex are recurrent themes in the literature. In contrast, dorsal aspects of the PFC tend to display hypometabolism. Ventriculomegaly and white matter hyperintensities are intimately associated with depression in elderly populations and likely have a vascular origin. Important confounding influences are medication, phenotypic and genetic heterogeneity, and technological limitations. We suggest that environmental stress and genetic risk variants interact with each other in a complex manner to alter neural circuitry and precipitate illness. Imaging genetic approaches hold out promise for advancing our understanding of affective illness.
Topics: Aging; Bipolar Disorder; Brain; Depressive Disorder, Major; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Models, Neurological; Positron-Emission Tomography; Stress, Psychological
PubMed: 19428491
DOI: 10.1016/j.neubiorev.2009.01.004 -
Biomedicine & Pharmacotherapy =... Oct 2023Lipid metabolism is a complex process that maintains the normal physiological function of the human body. The disorder of lipid metabolism has been implicated in various... (Review)
Review
Lipid metabolism is a complex process that maintains the normal physiological function of the human body. The disorder of lipid metabolism has been implicated in various human diseases, such as cardiovascular diseases and bone diseases. Intervertebral disc degeneration (IDD), an age-related degenerative disease in the musculoskeletal system, is characterized by high morbidity, high treatment cost, and chronic recurrence. Lipid metabolism disorder may promote the pathogenesis of IDD, and the potential mechanisms are complex. Leptin, resistin, nicotinamide phosphoribosyltransferase (NAMPT), fatty acids, and cholesterol may promote the pathogenesis of IDD, while lipocalin, adiponectin, and progranulin (PGRN) exhibit protective activity against IDD development. Lipid metabolism disorder contributes to extracellular matrix (ECM) degradation, cell apoptosis, and cartilage calcification in the intervertebral discs (IVDs) by activating inflammatory responses, endoplasmic reticulum (ER) stress, and oxidative stress and inhibiting autophagy. Several lines of agents have been developed to target lipid metabolism disorder. Inhibition of lipid metabolism disorder may be an effective strategy for the therapeutic management of IDD. However, an in-depth understanding of the molecular mechanism of lipid metabolism disorder in promoting IDD development is still needed.
Topics: Humans; Intervertebral Disc Degeneration; Lipid Metabolism; Lipid Metabolism Disorders; Adiponectin; Apoptosis
PubMed: 37651799
DOI: 10.1016/j.biopha.2023.115401 -
International Review of Neurobiology 2022Essential tremor (ET) is a highly prevalent neurologic disease and is the most common of the many tremor disorders. ET is a progressive condition with marked clinical...
Essential tremor (ET) is a highly prevalent neurologic disease and is the most common of the many tremor disorders. ET is a progressive condition with marked clinical heterogeneity, associated with a spectrum of both motor and non-motor features. However, its disease mechanisms remain poorly understood. Much debate has centered on whether ET should be considered a degenerative disorder, with underlying pathological changes in brain causing progressive disease manifestations, or an electric disorder, with overactivity of intrinsically oscillatory motor networks that occur without underlying structural brain abnormalities. Converging data from clinical, neuroimaging and pathological studies in ET now provide considerable evidence for the neurodegenerative hypothesis. A major turning point in this debate is that rigorous tissue-based studies have recently identified a series of structural changes in the ET cerebellum. Most of these pathological changes are centered on the Purkinje cell and connected neuronal populations, which can result in partial loss of Purkinje cells and circuitry reorganizations that would disturb cerebellar function. There is significant overlap in clinical and pathological features of ET with other disorders of cerebellar degeneration, and an increased risk of developing other degenerative diseases in ET. The combined implication of these studies is that ET could be degenerative. The evidence in support of the degenerative hypothesis is presented.
Topics: Cerebellum; Essential Tremor; Humans; Neurons; Purkinje Cells; Tremor
PubMed: 35750370
DOI: 10.1016/bs.irn.2022.02.003 -
Regenerative Therapy Dec 2020Osteoarthritis () is the most common chronic musculoskeletal disorder. It can affect any joint and is the most frequent single cause of disability in older adults. is a... (Review)
Review
Osteoarthritis () is the most common chronic musculoskeletal disorder. It can affect any joint and is the most frequent single cause of disability in older adults. is a progressive degenerative disease involving the entire joint structure in a vicious circle that includes the capsule-bursa tissue inflammation, synovial fluid modifications, cartilage breakdown and erosions, osteochondral inflammatory damage leading to bone erosion and distortion. Research has identified the initial inflammatory-immunologic process that starts this vicious cycle leading to so-called Research has also identified the role played in the disease advancement by synoviocytes and , chondrocytes, extracellular matrix, local immune-inflammatory mediators and proteases. This article investigates the joint-resident that play an essential local homeostatic role and regulate cell turn over and tissue repair. Resident establish and maintain a local . The understanding of physiopathology clarifies the core mechanisms by which minimally invasive interventions might be able to halt and reverse the course of early stage . Interventions employing , and are considered in this article.
PubMed: 33426213
DOI: 10.1016/j.reth.2020.07.007 -
Strabismus Mar 2018A spherical globe is traditionally assumed, but this study employed magnetic resonance imaging (MRI) to demonstrate frequent occurrence of non-spherical staphylomata in...
INTRODUCTION
A spherical globe is traditionally assumed, but this study employed magnetic resonance imaging (MRI) to demonstrate frequent occurrence of non-spherical staphylomata in strabismic patients.
METHODS
High-resolution, surface coil MRI was obtained in multiple image planes in 21 highly myopic subjects (36 eyes) and compared with 17 normal controls (33 eyes). Images were analyzed for axial length, aspect ratio of eye shape, and deflection of muscle paths.
RESULTS
All but two high myopes had strabismus. While myopic globes were generally spherical in 10 myopic eyes including both orthotropic subjects, 15 globes exhibited diffuse posterior staphylomata, 16 equatorial staphylomata, and 4 both posterior and equatorial staphylomata. Equatorial scleral ectasias were positioned to contact and elongate paths of horizontal rectus muscles in some gaze positions. Axial length in myopes averaged 28.8 ± 3.8 (SD) mm and did not differ significantly between regular vs. irregular staphylomata. Globe aspect ratios in the coronal, axial, and sagittal planes were significantly greater than normal in myopes (P < 0.005), but correlated significantly with axial length only in the axial and sagittal planes (P < 0.03). While myopes with irregular staphylomata were older at 57 ± 11 years than subjects with spherical globes at 24 ± 8 years (P < 0.0005), other clinical features were similar.
CONCLUSION
Irregular equatorial or posterior staphylomata are common in strabismic axial high myopes, acting, like "cams" affixed to the normally spherical globe so that they may have no mechanical effect until rotating eccentrically against muscles. After rotational contact, staphylomata would nonlinearly increase muscle tension with further duction. Imaging may be clinically informative about this "knobby eye syndrome."
Topics: Adult; Aged; Axial Length, Eye; Dilatation, Pathologic; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myopia, Degenerative; Oculomotor Muscles; Scleral Diseases; Strabismus; Syndrome
PubMed: 29279023
DOI: 10.1080/09273972.2017.1418393 -
Cells Jul 2021Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary... (Review)
Review
Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel developments in the field.
Topics: Animals; Axonemal Dyneins; Cilia; Ciliopathies; Cytoplasmic Dyneins; Humans; Kartagener Syndrome; Polymorphism, Genetic; Short Rib-Polydactyly Syndrome
PubMed: 34440654
DOI: 10.3390/cells10081885