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Current Opinion in Neurology Oct 2023
Topics: Humans; Cognition Disorders; Cognition
PubMed: 37678340
DOI: 10.1097/WCO.0000000000001201 -
Journal of Cellular and Molecular... Dec 2023Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can... (Review)
Review
Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.
Topics: Ghrelin; Growth Hormone; Human Growth Hormone
PubMed: 37661635
DOI: 10.1111/jcmm.17944 -
Indian Journal of Orthopaedics Dec 2023Osteoporosis is an age-related metabolic disease which has a significant impact on bone health and overall quality of life. It is gaining importance as a major medical... (Review)
Review
BACKGROUND
Osteoporosis is an age-related metabolic disease which has a significant impact on bone health and overall quality of life. It is gaining importance as a major medical consideration with the rapid increase in geriatric population globally. It increases the risk of vertebral fractures, progressive spinal deformities and neurological complications, contributing significantly to morbidity and mortality. Increase in life expectancy and advancement of medical technology has led to an increase in the proportion of geriatric patients undergoing orthopaedic procedures. It is becoming vital to adequately evaluate, investigate and treat osteoporosis before planning spinal surgery, especially spinal fusions and instrumentation.
CONTENT
Historically, osteoporosis was considered a contraindication to spine surgery adding to the burden of Disability Adjusted Life Years (DALYs) and mortality. Conversely, osteoporotic patients who underwent spine surgery were not adequately optimized, leading to an increase in failure and complication rates. Better understanding of the pathophysiology of osteoporosis and the biomechanics of an osteoporotic spine with knowledge of current standards of treatment of osteoporosis facilitate the timely and adequate management of this disease. Advances in surgical and anaesthetic techniques facilitate successful surgeries on high-risk elderly and osteoporotic patients with multiple comorbidities allowing for a significantly high predictability for long-term positive outcomes.This article discusses the biomechanics of the osteoporotic spine, the diagnosis and management of osteoporotic patients with spinal disease, and the new treatments, recommendations, surgical indications, strategies and advances in instrumentation in patients with osteoporosis who require spinal surgery.
IMPLICATIONS
In this article, the authors aim to provide a generalized overview for better understanding of the pathophysiological processes underlying osteoporosis in the vertebral column. This review provides a comprehensive set of guidelines for overall health and management of spine patients with pathologies, either caused by or compounded with osteoporosis. An overview of current techniques, strategies and technologies designed to address the challenges associated with spine surgery in osteoporotic patients is also outlined.
SOURCES
Content for this article has been sourced from routinely cited articles available via PubMed, from National Institute of Health consensus development conference, from the recommendations by World Health Organization technical report series, from previous articles by the authors and from the protocols established by the authors in their clinical practice based on experience and detailed case reviews.
PubMed: 38107796
DOI: 10.1007/s43465-023-01046-7 -
Presse Medicale (Paris, France : 1983) Jun 2024Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity... (Review)
Review
Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity disorders responsible for numbness, tingling, and loss of feeling are part and parcel of diabetic foot syndrome and require investigation in view of preventing trophic ulcers. To date, there exists no specific treatment for diabetic neuropathy possibly preventable by careful control of metabolic disorder. Effective management of diabetic patients would make it possible to limit the dramatic consequences of diabetic neuropathy while at the same time acting on other complications.
Topics: Humans; Diabetic Neuropathies; Diabetic Foot
PubMed: 38663725
DOI: 10.1016/j.lpm.2024.104236 -
Journal of Neurochemistry Oct 2023Cognitive deficits are a common comorbidity with neurological disorders and normal aging. Inflammation is associated with multiple diseases including classical... (Review)
Review
Cognitive deficits are a common comorbidity with neurological disorders and normal aging. Inflammation is associated with multiple diseases including classical neurodegenerative dementias such as Alzheimer's disease (AD) and autoimmune disorders such as multiple sclerosis (MS), in which over half of all patients experience some form of cognitive deficits. Other degenerative diseases of the central nervous system (CNS) including frontotemporal lobe dementia (FTLD), and Parkinson's disease (PD) as well as traumatic brain injury (TBI) and psychological disorders like major depressive disorder (MDD), and even normal aging all have cytokine-associated reductions in cognitive function. Thus, there is likely commonality between these secondary cognitive deficits and inflammation. Neurological disorders are increasingly associated with substantial neuroinflammation, in which CNS-resident cells secrete cytokines and chemokines such as tumor necrosis factor (TNF)α and interleukins (ILs) including IL-1β and IL-6. CNS-resident cells also respond to a wide variety of cytokines and chemokines, which can have both direct effects on neurons by changing the expression of ion channels and perturbing electrical properties, as well as indirect effects through glia-glia and immune-glia cross-talk. There is significant overlap in these cytokine and chemokine expression profiles across diseases, with TNFα and IL-6 strongly associated with cognitive deficits in multiple disorders. Here, we review the involvement of various cytokines and chemokines in AD, MS, FTLD, PD, TBI, MDD, and normal aging in the absence of dementia. We propose that the neuropsychiatric phenotypes observed in these disorders may be at least partially attributable to a dysregulation of immunity resulting in pathological cytokine and chemokine expression from both CNS-resident and non-resident cells.
PubMed: 37899543
DOI: 10.1111/jnc.15999 -
Journal of Translational Medicine Jan 2024NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a pivotal role in the regulation of neuronal function and synaptic plasticity, cellular adaptation to oxidative stress,... (Review)
Review
NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a pivotal role in the regulation of neuronal function and synaptic plasticity, cellular adaptation to oxidative stress, neuroinflammatory and degenerative processes, and tumorigenesis in the central nervous system (CNS). Impairment of the NQO1 activity in the CNS can result in abnormal neurotransmitter release and clearance, increased oxidative stress, and aggravated cellular injury/death. Furthermore, it can cause disturbances in neural circuit function and synaptic neurotransmission. The abnormalities of NQO1 enzyme activity have been linked to the pathophysiological mechanisms of multiple neurological disorders, including Parkinson's disease, Alzheimer's disease, epilepsy, multiple sclerosis, cerebrovascular disease, traumatic brain injury, and brain malignancy. NQO1 contributes to various dimensions of tumorigenesis and treatment response in various brain tumors. The precise mechanisms through which abnormalities in NQO1 function contribute to these neurological disorders continue to be a subject of ongoing research. Building upon the existing knowledge, the present study reviews current investigations describing the role of NQO1 dysregulations in various neurological disorders. This study emphasizes the potential of NQO1 as a biomarker in diagnostic and prognostic approaches, as well as its suitability as a target for drug development strategies in neurological disorders.
Topics: Humans; Alzheimer Disease; Brain Neoplasms; Carcinogenesis; NAD(P)H Dehydrogenase (Quinone); Neurons; Oxidative Stress; Brain Diseases
PubMed: 38167027
DOI: 10.1186/s12967-023-04802-3 -
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 -
Science Advances Aug 2023Mitochondrial permeability transition pore (MPTP) formation contributes to ischemia-reperfusion injury in the heart and several degenerative diseases, including muscular...
Mitochondrial permeability transition pore (MPTP) formation contributes to ischemia-reperfusion injury in the heart and several degenerative diseases, including muscular dystrophy (MD). MD is a family of genetic disorders characterized by progressive muscle necrosis and premature death. It has been proposed that the MPTP has two molecular components, the adenine nucleotide translocase (ANT) family of proteins and an unknown component that requires the chaperone cyclophilin D (CypD) to activate. This model was examined in vivo by deleting the gene encoding ANT1 () or CypD () in a δ-sarcoglycan () gene-deleted mouse model of MD, revealing that dystrophic mice lacking were partially protected from cell death and MD pathology. Dystrophic mice lacking both and together were almost completely protected from necrotic cell death and MD disease. This study provides direct evidence that ANT1 and CypD are required MPTP components governing in vivo cell death, suggesting a previously unrecognized therapeutic approach in MD and other necrotic diseases.
Topics: Animals; Mice; Muscular Dystrophies; Necrosis; Cell Death; Peptidyl-Prolyl Isomerase F; Disease Models, Animal
PubMed: 37624892
DOI: 10.1126/sciadv.adi2767 -
Biomedicine & Pharmacotherapy =... Dec 2023Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse... (Review)
Review
Degenerative musculoskeletal disorders are a group of age-related diseases of the locomotive system that severely affects the patient's ability to work and cause adverse sequalae such as fractures and even death. The incidence and prevalence of degenerative musculoskeletal disorders is rising owing to the aging of the world's population. The Notch signaling pathway, which is expressed in almost all organ systems, extensively regulates cell proliferation and differentiation as well as cellular fate. Notch signaling shows increased activity in degenerative musculoskeletal disorders and retards the progression of degeneration to some extent. The review focuses on four major degenerative musculoskeletal disorders (osteoarthritis, intervertebral disc degeneration, osteoporosis, and sarcopenia) and summarizes the pathophysiological functions of Notch signaling in these disorders, especially its role in stem/progenitor cells in each disorder. Finally, a conclusion will be presented to explore the research and application of the perspectives on Notch signaling in degenerative musculoskeletal disorders.
Topics: Humans; Intervertebral Disc Degeneration; Signal Transduction; Osteoarthritis; Aging; Osteoporosis
PubMed: 37981460
DOI: 10.1016/j.biopha.2023.115884