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Frontiers in Aging Neuroscience 2022Although primary degenerative diseases are the main cause of dementia, a non-negligible proportion of patients is affected by a secondary and potentially treatable... (Review)
Review
Although primary degenerative diseases are the main cause of dementia, a non-negligible proportion of patients is affected by a secondary and potentially treatable cognitive disorder. Therefore, diagnostic tools able to early identify and monitor them and to predict the response to treatment are needed. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological technique capable of evaluating and in "real time" the motor areas, the cortico-spinal tract, and the neurotransmission pathways in several neurological and neuropsychiatric disorders, including cognitive impairment and dementia. While consistent evidence has been accumulated for Alzheimer's disease, other degenerative cognitive disorders, and vascular dementia, to date a comprehensive review of TMS studies available in other secondary dementias is lacking. These conditions include, among others, normal-pressure hydrocephalus, multiple sclerosis, celiac disease and other immunologically mediated diseases, as well as a number of inflammatory, infective, metabolic, toxic, nutritional, endocrine, sleep-related, and rare genetic disorders. Overall, we observed that, while in degenerative dementia neurophysiological alterations might mirror specific, and possibly primary, neuropathological changes (and hence be used as early biomarkers), this pathogenic link appears to be weaker for most secondary forms of dementia, in which neurotransmitter dysfunction is more likely related to a systemic or diffuse neural damage. In these cases, therefore, an effort toward the understanding of pathological mechanisms of cognitive impairment should be made, also by investigating the relationship between functional alterations of brain circuits and the specific mechanisms of neuronal damage triggered by the causative disease. Neurophysiologically, although no distinctive TMS pattern can be identified that might be used to predict the occurrence or progression of cognitive decline in a specific condition, some TMS-associated measures of cortical function and plasticity (such as the short-latency afferent inhibition, the short-interval intracortical inhibition, and the cortical silent period) might add useful information in most of secondary dementia, especially in combination with suggestive clinical features and other diagnostic tests. The possibility to detect dysfunctional cortical circuits, to monitor the disease course, to probe the response to treatment, and to design novel neuromodulatory interventions in secondary dementia still represents a gap in the literature that needs to be explored.
PubMed: 36225892
DOI: 10.3389/fnagi.2022.995000 -
International Journal of Nanomedicine 2023Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic... (Review)
Review
Exosomes, as natural nanocarriers, characterized with low immunogenicity, non-cytotoxicity and targeted delivery capability, which have advantages over synthetic nanocarriers. Recently, exosomes have shown great potential as diagnostic markers for diseases and are also considered as a promising cell-free therapy. Engineered exosomes have significantly enhanced the efficacy and precision of delivering therapeutic agents, and are currently being extensively employed in targeted therapeutic investigations for various ailments, including oncology, inflammatory disorders, and degenerative conditions. Particularly, engineered exosomes enable therapeutic agent loading, targeted modification, evasion of MPS phagocytosis, intelligent control, and bioimaging, and have been developed as multifunctional nano-delivery platforms in recent years. The utilization of bioactive scaffolds that are loaded with exosome delivery has been shown to substantially augment retention, extend exosome release, and enhance efficacy. This approach has advanced from conventional hydrogels to nanocomposite hydrogels, nanofiber hydrogels, and 3D printing, resulting in superior physical and biological properties that effectively address the limitations of natural scaffolds. Additionally, plant-derived exosomes, which can participate in gut flora remodeling via oral administration, are considered as an ideal delivery platform for the treatment of intestinal diseases. Consequently, there is great interest in exosomes and exosomes as nanocarriers for therapeutic and diagnostic applications. This comprehensive review provides an overview of the biogenesis, composition, and isolation methods of exosomes. Additionally, it examines the pathological and diagnostic mechanisms of exosomes in various diseases, including tumors, degenerative disorders, and inflammatory conditions. Furthermore, this review highlights the significance of gut microbial-derived exosomes. Strategies and specific applications of engineered exosomes and bioactive scaffold-loaded exosome delivery are further summarized, especially some new techniques such as large-scale loading technique, macromolecular loading technique, development of multifunctional nano-delivery platforms and nano-scaffold-loaded exosome delivery. The potential benefits of using plant-derived exosomes for the treatment of gut-related diseases are also discussed. Additionally, the challenges, opportunities, and prospects of exosome-based nanocarriers for disease diagnosis and treatment are summarized from both preclinical and clinical viewpoints.
Topics: Exosomes; Administration, Oral; Cell- and Tissue-Based Therapy; Gastrointestinal Microbiome; Hydrogels
PubMed: 37635911
DOI: 10.2147/IJN.S417422 -
Cells Sep 2022Aging is a complex feature and involves loss of multiple functions and nonreversible phenotypes. However, several studies suggest it is possible to protect against aging... (Review)
Review
Aging is a complex feature and involves loss of multiple functions and nonreversible phenotypes. However, several studies suggest it is possible to protect against aging and promote rejuvenation. Aging is associated with many factors, such as telomere shortening, DNA damage, mitochondrial dysfunction, and loss of homeostasis. The integrity of the cytoskeleton is associated with several cellular functions, such as migration, proliferation, degeneration, and mitochondrial bioenergy production, and chronic disorders, including neuronal degeneration and premature aging. Cytoskeletal integrity is closely related with several functional activities of cells, such as aging, proliferation, degeneration, and mitochondrial bioenergy production. Therefore, regulation of cytoskeletal integrity may be useful to elicit antiaging effects and to treat degenerative diseases, such as dementia. The actin cytoskeleton is dynamic because its assembly and disassembly change depending on the cellular status. Aged cells exhibit loss of cytoskeletal stability and decline in functional activities linked to longevity. Several studies reported that improvement of cytoskeletal stability can recover functional activities. In particular, microtubule stabilizers can be used to treat dementia. Furthermore, studies of the quality of aged oocytes and embryos revealed a relationship between cytoskeletal integrity and mitochondrial activity. This review summarizes the links of cytoskeletal properties with aging and degenerative diseases and how cytoskeletal integrity can be modulated to elicit antiaging and therapeutic effects.
Topics: Cellular Senescence; Cytoskeleton; Dementia; Humans; Telomere Shortening
PubMed: 36139471
DOI: 10.3390/cells11182896 -
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 -
Cureus Feb 2023Age-related macular degeneration (AMD) is a highly prevalent macular condition that primarily affects the older population. It is the primary cause of blindness amongst... (Review)
Review
Age-related macular degeneration (AMD) is a highly prevalent macular condition that primarily affects the older population. It is the primary cause of blindness amongst the elderly population. It is an inflammatory disease that characteristically shows choroidal neovascularization and geographic atrophy. The exact pathomechanism of developing AMD is not known. However, certain factors such as increased age, smoking, genetic factors and certain environmental factors are usually associated with the development of the disease. AMD also involves oxidative stress-mediated destruction of retinal pigment epithelial cells and, consequently, that of retinal photoreceptors. Alzheimer's disease (AD) is a degenerative disorder involving the nervous system that usually affects people aged 65 and over. Both AMD and AD are age-related, degenerative conditions that have several similarities and share many of the same risk factors such as vascular conditions like arteriosclerosis, high blood pressure and obesity. It is believed that the early emergence of the clinical manifestations of AMD and AD may also be significantly influenced by oxidative stress and genetic polymorphism in complement factor H. A common pathogenic pathway between AD and AMD is quite likely. Amyloid-β is an aberrant protein that accumulates within the brains of Alzheimer's patients and appears as plaques on magnetic resonance imaging (MRI). These plaques are a pathognomonic sign of Alzheimer's disease. Similar to this, amyloid-β deposits are reported to build up beneath the retina of AMD patients, which appear as tiny clusters of protein-lipid substances known as drusen. It has also been found that individuals suffering from AMD exhibit an increased chance of developing AD than those with no AMD.
PubMed: 36938233
DOI: 10.7759/cureus.34920 -
Quantitative Imaging in Medicine and... Dec 2020Despite the growing use of computed tomography (CT) and magnetic resonance imaging (MRI) in the study of spinal disorders, radiography still plays an important role in... (Review)
Review
Despite the growing use of computed tomography (CT) and magnetic resonance imaging (MRI) in the study of spinal disorders, radiography still plays an important role in many conditions affecting the spine. However, the study and interpretation of spine radiograph is receiving less attention and radiologists are increasingly unfamiliar with the typical findings in normal and pathologic conditions of the spine. The aim of this article is to review the radiologic indications of radiograph in different pathologic conditions that affect the spine, including congenital, traumatic, degenerative, inflammatory, infectious and tumour disorders, as well as their main radiographic manifestations.
PubMed: 33269230
DOI: 10.21037/qims-20-1014 -
Current Treatment Options in... 2021Valvular heart disease is prevalent in older athletes with primarily degenerative valvular disorders and younger athletes with congenital or genetic syndromes. Limited...
Valvular heart disease is prevalent in older athletes with primarily degenerative valvular disorders and younger athletes with congenital or genetic syndromes. Limited data exist on the risks and benefits of exercise for athletes with underlying valvular disorders, so current guidelines are primarily based upon expert consensus. This review focuses on the current data, guideline recommendations, and emerging clinical conundrums for athletes with common valvular heart conditions including aortic stenosis, bicuspid aortic valve (BAV), mitral regurgitation (MR), mitral valve prolapse (MVP), and thoracic aortic aneurysms.
PubMed: 35356384
DOI: 10.1007/s11936-021-00950-1 -
Brain Sciences Jul 2021Parkinson's disease (PD) is a progressive, degenerative disorder that affects 10 million people worldwide. More than 90% of individuals with PD develop hypokinetic... (Review)
Review
Parkinson's disease (PD) is a progressive, degenerative disorder that affects 10 million people worldwide. More than 90% of individuals with PD develop hypokinetic dysarthria, a motor speech disorder that impairs vocal communication and quality of life. Despite the prevalence of vocal deficits in this population, very little is known about the pathological mechanisms underlying this aspect of disease. As such, effective treatment options are limited. Rat models have provided unique insights into the disease-specific mechanisms of vocal deficits in PD. This review summarizes recent studies investigating vocal deficits in 6-hydroxydopamine (6-OHDA), alpha-synuclein overexpression, , and rat models of PD. Model-specific changes to rat ultrasonic vocalization (USV), and the effects of exercise and pharmacologic interventions on USV production in these models are discussed.
PubMed: 34356159
DOI: 10.3390/brainsci11070925 -
Journal of Cerebral Blood Flow and... Aug 2021Alzheimer's disease (AD) is a devastating neurological degenerative disorder and is the most common cause of dementia in the elderly. Clinically, AD manifests with... (Review)
Review
Alzheimer's disease (AD) is a devastating neurological degenerative disorder and is the most common cause of dementia in the elderly. Clinically, AD manifests with memory and cognitive decline associated with deposition of hallmark amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although the mechanisms underlying AD remains unclear, two hypotheses have been proposed. The established amyloid hypothesis states that Aβ accumulation is the basis of AD and leads to formation of NFTs. In contrast, the two-hit vascular hypothesis suggests that early vascular damage leads to increased accumulation of Aβ deposits in the brain. Multiple studies have reported significant morphological changes of the cerebrovasculature which can result in severe functional deficits. In this review, we delve into known structural and functional vascular alterations in various mouse models of AD and the cellular and molecular constituents that influence these changes to further disease progression. Many studies shed light on the direct impact of Aβ on the cerebrovasculature and how it is disrupted during the progression of AD. However, more research directed towards an improved understanding of how the cerebrovasculature is modified over the time course of AD is needed prior to developing future interventional strategies.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cerebral Amyloid Angiopathy; Cerebrovascular Circulation; Disease Models, Animal; Mice, Transgenic; Neurofibrillary Tangles; Phenotype
PubMed: 33557692
DOI: 10.1177/0271678X21992462 -
International Journal of Environmental... Jul 2021Temporomandibular disorders (TMD) are a common reason for patients to present at dental offices. The majority of people with TMD are women between the age of 20 and 40...
BACKGROUND
Temporomandibular disorders (TMD) are a common reason for patients to present at dental offices. The majority of people with TMD are women between the age of 20 and 40 years. The purpose of this study was to assess the types and prevalence of temporomandibular disorders in female patients of reproductive age with menstrual disorders.
MATERIALS AND METHODS
The study involved 65 females of reproductive age (18-40 years, an average of 28.00 ± 6.27 years). The women who qualified for the study were patients of the University Center for Maternal and Newborn's Health hospitalized because of infertility or menstrual cycle disorders. Women with confirmed estrogen metabolism disorders participated in a clinical study with the use of Diagnostic Criteria for Temporomandibular Disorders (DC/TMD).
RESULTS
In the studied female patients with menstrual disorders, temporomandibular disorders (92.3%) were frequent occurrences. The most common type was intra-articular joint disorders (68%). Other reported complaints included masticatory muscle pain (44.62%), and degenerative joint diseases (12.3%).
CONCLUSIONS
1. In women with menstrual disorders, TMD may exist. 2. In women with TMD symptoms, their medical history should be extended to include the diagnosis of female hormone disorders.
Topics: Adult; Facial Pain; Female; Humans; Infant, Newborn; Male; Masticatory Muscles; Menstruation Disturbances; Myalgia; Prevalence; Temporomandibular Joint Disorders; Young Adult
PubMed: 34299715
DOI: 10.3390/ijerph18147263