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International Journal of Molecular... May 2024Oxidative stress and inflammation are recognized as pivotal contributors and common features of several chronic degenerative diseases, including cancer, metabolic...
Oxidative stress and inflammation are recognized as pivotal contributors and common features of several chronic degenerative diseases, including cancer, metabolic syndrome, type 2 diabetes, cardiovascular diseases and neurodegenerative disorders, affecting a high percentage of the population [...].
Topics: Oxidative Stress; Humans; Inflammation; Neurodegenerative Diseases; Chronic Disease; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Animals; Metabolic Syndrome
PubMed: 38732245
DOI: 10.3390/ijms25095026 -
Cureus Sep 2023To diagnose and predict the possibility of Alzheimer's or a different kind of dementia, medical professionals employ tests that look at a patient's mental competence;... (Review)
Review
To diagnose and predict the possibility of Alzheimer's or a different kind of dementia, medical professionals employ tests that look at a patient's mental competence; however, such methods are impracticable. A reliable diagnosis at the start of treatment is essential for therapy. Except in situations with apparent genetic variations, most Alzheimer's patients lack a known etiology. Therefore, every Alzheimer's patient receives the same treatment plan, regardless of the etiology, which may or may not be successful in slowing or preventing the disease's progression. Tau pathology is further complicated by the amyloid buildup that arises from the cellular phase of Alzheimer's disease (AD). Alzheimer's is a degenerative, diverse, complicated, and incurable neurological disorder primarily affecting elderly individuals. The currently accepted drugs available for treating AD, which involve cholinesterase inhibitors and N-methyl-D-aspartate NMDA)-receptor antagonists only provide temporary relief from symptoms. The neurological disorder primarily affecting elderly individuals is degenerative, diverse, complicated, and incurable. Accurate diagnosis is the most essential prerequisite before beginning therapy. Most Alzheimer's patients' causes are still unclear, except for instances where hereditary variations have been noted. The gut microbiota composition significantly influences AD and any age-associated neurological illness. Therapies are very useful in improving the cognitive functions of AD. New microbiota-based therapy alternatives may now be available due to the more recent connection between the altered gut microbiome and neurodegeneration through the gut microbiota-brain axis.
PubMed: 37868425
DOI: 10.7759/cureus.45649 -
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 -
Journal of Nanobiotechnology Aug 2023The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous...
The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.
Topics: Mice; Animals; Nanogels; Depression; Reactive Oxygen Species; Exosomes; Perimenopause; Pituitary Adenylate Cyclase-Activating Polypeptide; Drug Carriers
PubMed: 37553718
DOI: 10.1186/s12951-023-02005-y -
Molecules (Basel, Switzerland) Mar 2024Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and... (Review)
Review
Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.
Topics: Humans; Alzheimer Disease; Microglia; Neuroinflammatory Diseases; Central Nervous System; Anti-Inflammatory Agents
PubMed: 38611758
DOI: 10.3390/molecules29071478 -
Cerebellum (London, England) Nov 2023With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment... (Review)
Review
With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.
PubMed: 37955812
DOI: 10.1007/s12311-023-01625-2 -
Survey of Ophthalmology Apr 2024Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial... (Review)
Review
Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways.
PubMed: 38679146
DOI: 10.1016/j.survophthal.2024.04.004 -
Frontiers in Bioscience (Landmark... Nov 2023As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson's disease (PD) is very complex, and...
BACKGROUND
As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson's disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons are affected and microglia are activated.
METHODS
A theoretical protein-RNA recognition code that assumes that the second letter in codons is compatible with specific amino acids involved in protein-RNA recognition was used to search for compatibility of human α-synuclein (α-syn) with mRNAs in the human transcriptome (1-L transcription).
RESULTS
The 1-L transcription revealed compatible amino acid sequences with the ATTTA ARE (class I), PAS and polyA in α-syn, supporting a protein-RNA regulatory model. In PD, inflammatory microglia reactions, cognitive decline and motor circuit disturbances are observed. The model theoretically explains why α-syn producing neurons are less protected from inflammation and why microglia are activated. Consistent with knowledge of PD, the identified genes showed how the PI3K-AKT pathway is downregulated, how reactive oxygen species (ROS) production and sensitivity are increased, how mitochondria are destabilized, why autophagy is impaired, and why neuronal depigmentation is observed.
CONCLUSIONS
1-L transcription of α-syn leads to genes/proteins relevant to PD. When α-syn is accepted as a small RNA recognition protein involved in the post-transcriptional regulations, some identified genes indicate that its function is an important regulatory factor associated with intracellular and extracellular transport of RNA vesicles. These vesicles are extremely important in cellular communication. In addition, the spectrum of identified genes strongly indicates that α-syn produced by neuronal cells is required for proper regulation of inflammatory and immune responses.
Topics: Humans; Parkinson Disease; Phosphatidylinositol 3-Kinases; alpha-Synuclein; Gene Expression Regulation; Inflammation; Dopaminergic Neurons; RNA
PubMed: 38062843
DOI: 10.31083/j.fbl2811292 -
Osteoporosis and depression in perimenopausal women: From clinical association to genetic causality.Journal of Affective Disorders Jul 2024Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes...
BACKGROUND
Osteoporosis and major depressive disorder (MDD) represent two significant health challenges globally, particularly among perimenopausal women. This study utilizes NHANES data and Mendelian randomization (MR) analysis to explore the link between them, aiming to provide a basis for intervention strategies for this group.
METHODS
The study analyzed NHANES 2007-2018 data using weighted logistic regression in R software to evaluate the link between MDD and osteoporosis risk. Then, a two-sample MR analysis with GWAS summary statistics was performed, mainly using the IVW method. Additional validation included MR Egger, Weighted Median, Mode, and MR-PRESSO methods.
RESULTS
The research analysis indicated a significant link between MDD and the risk of osteopenia/osteoporosis. Our analysis revealed a significant positive relationship between MDD and both femoral neck osteoporosis (OR = 6.942 [95 % CI, 1.692-28.485]) and trochanteric osteoporosis (OR = 4.140 [95 % CI, 1.699-10.089]). In analyses related to osteopenia, a significant positive correlation was observed between MDD and both total femoral osteopenia (OR = 3.309 [95 % CI, 1.577-6.942]) and trochanteric osteopenia (OR = 2.467 [95 % CI, 1.004-6.062]). Furthermore, in the MR analysis, genetically predicted MDD was causally associated with an increased risk of osteoporosis via the IVW method (P = 0.013).
LIMITATIONS
Our study was limited by potential selection bias due to excluding subjects with missing data, and its applicability was primarily to European and American populations.
CONCLUSION
Integrating NHANES and MR analyses, a robust correlation between MDD and osteoporosis was identified, emphasizing the significance of addressing this comorbidity within clinical practice and meriting further investigation.
Topics: Humans; Female; Depressive Disorder, Major; Perimenopause; Mendelian Randomization Analysis; Middle Aged; Osteoporosis; Genome-Wide Association Study; Nutrition Surveys; Bone Diseases, Metabolic; Risk Factors; Adult
PubMed: 38608764
DOI: 10.1016/j.jad.2024.04.019 -
Heliyon Oct 2023With the acceleration of the aging process of the population, the number of edentulous patients continuously increased. Edentulism induces the loss of occlusal... (Review)
Review
BACKGROUND
With the acceleration of the aging process of the population, the number of edentulous patients continuously increased. Edentulism induces the loss of occlusal relationship and cause adverse effects on the stomatognathic system. Temporomandibular joint (TMJ), as a significant component of this system, may also be affected by edentulism in the process of supporting mandibular movement.
PURPOSE
Provide a comprehensive review of the structure and function of TMJ in the edentulous population, as well as the prevalence of temporomandibular joint disorder (TMD) in edentulous group.
STUDY SELECTION
An electronic search was conducted on articles prior to December 2022 to filter all papers relevant to the structure and function of TMJ in edentulous population. The internet databases (PubMed, Cochrane Library, Embase) were searched using various combinations of keywords for "edentulism" or "edentulous" and "TMJ" or "TMD".
RESULTS
Firstly, 522 articles were selected from the internet database, and finally, a total of 44 articles met the inclusion and exclusion criteria. The research content of these articles mainly focuses on the structure and function of TMJ in edentulous patients, as well as the clinical signs and symptoms of TMD.
CONCLUSIONS
Edentulous arch induces the loss of occlusal relationship, which may lead to degenerative changes of TMJ components consisting of changes in morphology and bone mass density of condyle, articular fossa, and articular eminence. In addition, the condyle could be shifted backward and upward, and displacement of the articular disc may occur after dentition loss. And the condyle and the articular disc may be guided back to the normal position after effective prosthodontic treatment. But the conclusions of the study on the function of TMJ and the prevalence of TMD in edentulous people are inconsistent. The condition of TMJ, especially the position of condyle-fossa and the symptoms and signs of TMD should not be ignored. If necessary, radiographic examinations should be performed.
PubMed: 37829806
DOI: 10.1016/j.heliyon.2023.e20307