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Seminars in Cell & Developmental Biology Mar 2024Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its... (Review)
Review
Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its interactions with numerous extracellular matrix components, proteins and signaling molecules that enable its modulation to various physiological and pathological processes. Characterization of TSP-4 expression under development and pathogenesis of disorders has yielded important insights into mechanisms underlying the unique role of TSP-4 in mediating various processes including cell-cell, cell-extracellular matrix interactions, cell migration, proliferation, tissue remodeling, angiogenesis, and synaptogenesis. Maladaptation of these processes in response to pathological insults and stress can accelerate the development of disorders including skeletal dysplasia, osteoporosis, degenerative joint disease, cardiovascular diseases, tumor progression/metastasis and neurological disorders. Overall, the diverse functions of TSP-4 suggest that it may be a potential marker or therapeutic target for prognosis, diagnosis, and treatment of various pathological conditions upon further investigations. This review article highlights recent findings on the role of TSP-4 in both physiological and pathological conditions with a focus on what sets it apart from other TSPs.
Topics: Humans; Thrombospondins; Extracellular Matrix; Cell Movement; Morphogenesis; Cardiovascular Diseases
PubMed: 37391348
DOI: 10.1016/j.semcdb.2023.06.007 -
Frontiers in Microbiology 2023As society ages, the number of patients with spinal degenerative diseases (SDD) is increasing, posing a major socioeconomic problem for patients and their families. SDD... (Review)
Review
As society ages, the number of patients with spinal degenerative diseases (SDD) is increasing, posing a major socioeconomic problem for patients and their families. SDD refers to a generic term for degenerative diseases of spinal structures, including osteoporosis (bone), facet osteoarthritis (joint), intervertebral disk degeneration (disk), lumbar spinal canal stenosis (yellow ligament), and spinal sarcopenia (muscle). We propose the term "gut-spine axis" for the first time, given the influence of gut microbiota (GM) on the metabolic, immune, and endocrine environment in hosts through various potential mechanisms. A close cross-talk is noted between the aforementioned spinal components and degenerative diseases. This review outlines the nature and role of GM, highlighting GM abnormalities associated with the degeneration of spinal components. It also summarizes the evidence linking GM to various SDD. The gut-spine axis perspective can provide novel insights into the pathogenesis and treatment of SDD.
PubMed: 37965563
DOI: 10.3389/fmicb.2023.1290858 -
Frontiers in Bioengineering and... 2023The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury,... (Review)
Review
The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients' quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology.
PubMed: 37811372
DOI: 10.3389/fbioe.2023.1259731 -
Journal of Biomedical Science Sep 2023Mitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally... (Review)
Review
Mitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally inherited with 37 genes, encoding 13 polypeptides for oxidative phosphorylation, and 22 tRNAs and 2 rRNAs for translation. mtDNA mutations are associated with a wide spectrum of degenerative and neuromuscular diseases. However, the pathophysiology of mitochondrial diseases, especially for threshold effect and tissue specificity, is not well understood and there is no effective treatment for these disorders. Especially, the lack of appropriate cell and animal disease models has been significant obstacles for deep elucidating the pathophysiology of maternally transmitted diseases and developing the effective therapy approach. The use of human induced pluripotent stem cells (iPSCs) derived from patients to obtain terminally differentiated specific lineages such as inner ear hair cells is a revolutionary approach to deeply understand pathogenic mechanisms and develop the therapeutic interventions of mitochondrial disorders. Here, we review the recent advances in patients-derived iPSCs as ex vivo models for mitochondrial diseases. Those patients-derived iPSCs have been differentiated into specific targeting cells such as retinal ganglion cells and eventually organoid for the disease modeling. These disease models have advanced our understanding of the pathophysiology of maternally inherited diseases and stepped toward therapeutic interventions for these diseases.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Mutation; Mitochondria; Cell Differentiation; DNA, Mitochondrial
PubMed: 37737178
DOI: 10.1186/s12929-023-00967-7 -
Diagnostics (Basel, Switzerland) Mar 2024Cervical myelopathy is referred to in many ways in the English literature, for example, as (, () or (). In addition, more frequent occurrences are noted in older... (Review)
Review
Cervical myelopathy is referred to in many ways in the English literature, for example, as (, () or (). In addition, more frequent occurrences are noted in older adults and to a greater extent in men. The causes of the effects of cervical myelopathy may be the appearance of lesions on the spinal cord, ischemia due to compression of the vertebral artery and repeated micro-injuries during maximal movements-hyperflexion or hyperextension. It is well known that lesions on the spinal cord may occur in a quarter of the population, and this problem is clearly noted in people over 60 years old. The symptoms of SCM develop insidiously, and their severity and side (unilateral or bilateral) are associated with the location and extent of spinal cord compression. Neurological examination most often diagnoses problems in the upper limbs (most often paresis with developing hand muscle atrophy), pyramidal paralysis in one or both lower limbs and disorders in the urinary system. To make a diagnosis of CSM, it is necessary to perform MRI and neurophysiological tests (such as EMG or sensory and/or motor-evoked potentials). The use of appropriately selected scales and specific tests in diagnostics is also crucial. This narrative review article describes the latest knowledge on the diagnosis and clinimetrics of cervical spondylotic myelopathy in adults and provides future directions.
PubMed: 38473028
DOI: 10.3390/diagnostics14050556 -
JAMA Ophthalmology Dec 2023High myopia is a global concern due to its escalating prevalence and the potential risk of severe visual impairment caused by pathologic myopia. Using artificial...
IMPORTANCE
High myopia is a global concern due to its escalating prevalence and the potential risk of severe visual impairment caused by pathologic myopia. Using artificial intelligence to estimate future visual acuity (VA) could help clinicians to identify and monitor patients with a high risk of vision reduction in advance.
OBJECTIVE
To develop machine learning models to predict VA at 3 and 5 years in patients with high myopia.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, single-center, cohort study was performed on patients whose best-corrected VA (BCVA) at 3 and 5 years was known. The ophthalmic examinations of these patients were performed between October 2011 and May 2021. Thirty-four variables, including general information, basic ophthalmic information, and categories of myopic maculopathy based on fundus and optical coherence tomography images, were collected from the medical records for analysis.
MAIN OUTCOMES AND MEASURES
Regression models were developed to predict BCVA at 3 and 5 years, and a binary classification model was developed to predict the risk of developing visual impairment at 5 years. The performance of models was evaluated by discrimination metrics, calibration belts, and decision curve analysis. The importance of relative variables was assessed by explainable artificial intelligence techniques.
RESULTS
A total of 1616 eyes from 967 patients (mean [SD] age, 58.5 [14.0] years; 678 female [70.1%]) were included in this analysis. Findings showed that support vector machines presented the best prediction of BCVA at 3 years (R2 = 0.682; 95% CI, 0.625-0.733) and random forest at 5 years (R2 = 0.660; 95% CI, 0.604-0.710). To predict the risk of visual impairment at 5 years, logistic regression presented the best performance (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.816-0.912). The baseline BCVA (logMAR odds ratio [OR], 0.298; 95% CI, 0.235-0.378; P < .001), prior myopic macular neovascularization (OR, 3.290; 95% CI, 2.209-4.899; P < .001), age (OR, 1.578; 95% CI, 1.227-2.028; P < .001), and category 4 myopic maculopathy (OR, 4.899; 95% CI, 1.431-16.769; P = .01) were the 4 most important predicting variables and associated with increased risk of visual impairment at 5 years.
CONCLUSIONS AND RELEVANCE
Study results suggest that developing models for accurate prediction of the long-term VA for highly myopic eyes based on clinical and imaging information is feasible. Such models could be used for the clinical assessments of future visual acuity.
Topics: Humans; Female; Middle Aged; Cohort Studies; Retrospective Studies; Artificial Intelligence; Myopia; Visual Acuity; Retinal Diseases; Macular Degeneration; Vision, Low; Vision Disorders; Tomography, Optical Coherence; Machine Learning; Myopia, Degenerative
PubMed: 37883115
DOI: 10.1001/jamaophthalmol.2023.4786 -
Phytotherapy Research : PTR Feb 2024Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug... (Review)
Review
Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.
Topics: Humans; Central Nervous System; Anti-Inflammatory Agents; Acetophenones; Cerebrovascular Disorders; Paeonia
PubMed: 37872838
DOI: 10.1002/ptr.8049 -
Phytomedicine : International Journal... Dec 2023Neurodegenerative diseases are among the most common diseases in older adults worldwide. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common... (Review)
Review
BACKGROUND
Neurodegenerative diseases are among the most common diseases in older adults worldwide. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common neurodegenerative diseases, and are accompanied by cerebral cortical atrophy, neuronal loss, protein accumulation, and excessive accumulation of metal ions. Natural products exhibit outstanding performance in improving cerebral circulatory disorders, promoting cerebral haematoma absorption, repairing damaged nerve tissue, and improving damaged nerve function. In recent years, studies have shown that neuroinflammatory mechanisms and signalling pathways closely related to the occurrence and development of neurological diseases include microglial activation, nuclear factor-κB (NF-κB) pathway, mitogen activated protein kinases (MAPK) pathway, reactive oxygen pathway, nucleotide binding oligomerisation domain-like receptor protein3 (NLRP3) inflammasomes, toll-like receptor4 (TLR4) pathway, nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, and intestinal flora. Therefore, this study considered the mechanism of neurological diseases as the starting point to review the mechanism of action of natural products in the prevention and treatment of AD and PD in recent years to provide a theoretical basis for clinical prevention and treatment.
AIM
Natural products are a promising source of novel lead structures that have long been used to treat various nervous system diseases.
METHODOLOGY
This review collected literature on neurological diseases and natural products from 2012 to 2022, which were mainly searched through databases such as ScienceDirect, Springer, PubMed, SciFinder, China National Knowledge Infrastructure (CNKI), Wanfang, Google Scholar, and Baidu Academic. The following keywords were searched: neurological disorders, natural products, signalling pathway, mechanism of action.
RESULTS
This review summarises the pathogenesis of degenerative neurological diseases, recent findings on natural products used in neurodegenerative diseases, and the molecular mechanisms underlying these effects.
Topics: Humans; Aged; Neurodegenerative Diseases; Phosphatidylinositol 3-Kinases; Biological Products; Signal Transduction; NF-kappa B; Alzheimer Disease; Parkinson Disease
PubMed: 37778246
DOI: 10.1016/j.phymed.2023.155101 -
International Immunopharmacology Nov 2023Synovial inflammation and chondrocyte death have been widely acknowledged as key contributors to the pathological progression of temporomandibular joint osteoarthritis...
OBJECTIVES
Synovial inflammation and chondrocyte death have been widely acknowledged as key contributors to the pathological progression of temporomandibular joint osteoarthritis (TMJ-OA), a degenerative joint disease currently lacking definitive treatments. This study aims to understand the regulatory role of chondrocyte pyroptosis in condylar cartilage degradation during TMJ-OA.
METHODS
The levels of cytokines, cartilage degeneration markers, and pyroptotic biomarkers in the synovium and synovial fluid of temporomandibular disorders (TMD) patients were examined. The synovitis, cartilage degradation, and chondrocyte pyroptosis in wild-type and alpha-kinase 1 (ALPK1)-deficient TMJ-OA mice were then compared following monosodium iodoacetate (MIA) induction. Subsequently, we investigated the downstream mechanisms of cytokines- or macrophage supernatants-induced metabolic disorders and pyroptosis in chondrocytes using primary TMJ chondrocytes and ATDC5 chondrocyte cultures.
RESULTS
We found a positive correlation between pyroptotic biomarkers and cartilage degradation mediators and cytokines in the synovial fluid of TMD patients. MIA-induced TMJ-OA mice demonstrated significant synovitis, cartilage degradation, and chondrocyte pyroptosis, which were mitigated in ALPK1-deficient TMJ-OA mice, inflammation-restrained mice. Ex-vivo study revealed the contribution of reactive oxygen species (ROS) to inflammation-irritated macrophage supernatants-induced pyroptosis and metabolic disorders in chondrocytes. Targeting NOD-like receptor protein 3 (NLRP3) alleviated cytokines- or ROS-induced pyroptosis and metabolic disorders in chondrocytes by inhibiting caspase-1 activation and interleukin-1β (IL-1β) secretion.
CONCLUSION
Our findings offer novel insight into the role of synovial inflammation-induced chondrocyte pyroptosis in promoting cartilage degradation during TMJ-OA via the ROS and NLRP3 signaling pathway.
PubMed: 37625369
DOI: 10.1016/j.intimp.2023.110781