Young Exosome Bio‐Nanoparticles Restore Aging‐Impaired Tendon Stem/Progenitor Cell Function and Reparative Capacity

Advanced Materials, Год журнала: 2023, Номер 35(18)

Опубликована: Фев. 13, 2023

Aging impairs tendon stem/progenitor cell function and homeostasis, however, effective treatments for aging-induced diseases are lacking. Exosomes naturally derived nanoparticles that contain bioactive molecules, therefore, have attracted great interest in tissue engineering regenerative medicine. In this study, it is shown young exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED-Exos) possess abundant anti-aging signals. These bio-nanoparticles can alleviate the aging phenotypes of aged (AT-SCs) maintain their tenogenic capacity. Mechanistically, SHED-Exos modulate histone methylation inhibit nuclear factor-κB to reverse AT-SC aging. a mouse model, systemic administration SHED-Exo retards degeneration. Interestingly, local delivery SHED-Exos-loaded microspheres confers phenotypes, including reduced senescent decreased ectopic bone formation, thereby functionally structurally rescuing endogenous regeneration repair capacity rats. Overall, SHED-Exos, as natural nanoparticles, promising translational therapeutic potential aging-related diseases.

Язык: Английский

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A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 7, 2022

Cerebral infarction/ischemia-reperfusion injury is currently the disease with highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die ischemia several hours after ischemic stroke, which activates innate immune response in brain, promotes production neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species − nitrogen oxide, mediates destruction blood-brain barrier occurrence a series cascade reactions. Meanwhile, expression adhesion molecules cerebral vascular endothelial increased, polymorphonuclear neutrophils, lymphocytes mononuclear macrophages passed through entered brain tissue. These recognize antigens exposed by central nervous system activate adaptive responses, further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce above-mentioned body induces peripheral immunosuppressive responses negative feedback, increases incidence post-stroke infection. This process accompanied changes status tissue local systemic systems. A growing number implicate noncoding RNAs (ncRNAs) novel epigenetic regulatory elements dysfunction various cell subsets neurovascular unit injury. particular, recent revealed advances ncRNA biology greatly expand understanding regulation inflammation Identification aberrant patterns associated biological effects ncRNAs patients their potential biomarkers therapeutic targets for Therefore, this review systematically presents on involvement neuroimmune cascades, elucidates functions mechanisms infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities discovery targeted therapy. Furthermore, introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display possible transformative tool studying lncRNAs. future, expected be used target diagnosing injury, judging its prognosis treatment, thereby significantly improving patients.

Язык: Английский

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PICALM and Alzheimer’s Disease: An Update and Perspectives

Cells, Год журнала: 2022, Номер 11(24), С. 3994 - 3994

Опубликована: Дек. 10, 2022

Genome-wide association studies (GWAS) have identified the PICALM (Phosphatidylinositol binding clathrin-assembly protein) gene as most significant genetic susceptibility locus after APOE and BIN1. is a clathrin-adaptor protein that plays critical role in clathrin-mediated endocytosis autophagy. Since effects of variants AD-susceptibility loci been confirmed by independent several distinct cohorts, there has number vitro vivo attempting to elucidate underlying mechanism which modulates AD risk. While differential modulation APP processing Aβ transcytosis reported, tau pathology progression also evidenced Alzheimer’s disease models. In this review, we summarize current knowledge about PICALM, its physiological functions, variants, post-translational modifications relevance pathogenesis.

Язык: Английский

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Microglial phagocytosis and regulatory mechanisms after stroke

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2022, Номер 42(9), С. 1579 - 1596

Опубликована: Май 1, 2022

Stroke, including ischemic stroke and hemorrhagic can cause massive neuronal death disruption of brain structure, which is followed by secondary inflammatory injury initiated pro-inflammatory molecules cellular debris. Phagocytic clearance debris microglia, the brain’s scavenger cells, pivotal for neuroinflammation resolution neurorestoration. However, microglia also exacerbate loss phagocytosing stressed-but-viable neurons in penumbra, thereby expanding area hindering neurofunctional recovery. Microglia constantly patrol central nervous system using their processes to scour environment start or cease phagocytosis progress depending on “eat me” “don’t eat me’’ signals surface. An optimal immune response requires a delicate balance between different phenotypic states regulate neuro-inflammation facilitate reconstruction after stroke. Here, we examine literature discuss molecular mechanisms pathways regulating microglial phagocytosis, resulting effects neural regeneration, as well potential therapeutic targets that might modulate phagocytic activity improve neurological function

Язык: Английский

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Non-Coding RNAs as Novel Regulators of Neuroinflammation in Alzheimer’s Disease

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июнь 2, 2022

Alzheimer’s disease (AD) is one of the most common causes dementia. Although significant breakthroughs have been made in understanding progression and pathogenesis AD, it remains a worldwide problem public health burden. Thus, more efficient diagnostic therapeutic strategies are urgently required. The latest research studies revealed that neuroinflammation crucial AD. Non-coding RNAs (ncRNAs), including long noncoding (lncRNAs), microRNAs (miRNAs), circular (circRNAs), PIWI-interacting (piRNAs), transfer RNA-derived small (tsRNAs), strongly associated with AD-induced neuroinflammation. Furthermore, several ongoing pre-clinical currently investigating ncRNA as biomarkers interventions to provide new perspectives for AD diagnosis treatment. In this review, role different types ncRNAs during summarized order improve our etiology aid translation basic into clinical practice.

Язык: Английский

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An interplay between non-coding RNAs and gut microbiota in human health

Diabetes Research and Clinical Practice, Год журнала: 2023, Номер 201, С. 110739 - 110739

Опубликована: Июнь 1, 2023

Язык: Английский

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Neuroprotective Effects of Lactobacillus plantarum PS128 in a Mouse Model of Parkinson’s Disease: The Role of Gut Microbiota and MicroRNAs

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6794 - 6794

Опубликована: Апрель 5, 2023

Parkinson's disease (PD) is a neurodegenerative characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD complex mounting evidence has suggested an association with the dysregulation microRNAs (miRNAs) gut dysbiosis. Using rotenone-induced mouse model, we observed that administration Lactobacillus plantarum PS128 (PS128) significantly improved PD-like mice, accompanied increased level dopamine, reduced dopaminergic neuron loss, microglial activation, levels inflammatory factors, enhanced expression neurotrophic factor brain. Notably, inflammation-related miR-155-5p was upregulated proximal colon, midbrain, striatum mice. miR-155-5p, whereas it suppressor cytokine signaling 1 (SOCS1), direct target critical inhibitor response Alteration fecal microbiota mice partially restored administration. Among them, Bifidobacterium, Ruminiclostridium_6, Bacteroides, Alistipes were statistically correlated improvement SOCS1. Our findings ameliorates exerts neuroprotective effects regulating miR-155-5p/SOCS1 pathway

Язык: Английский

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The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(14), С. 4130 - 4130

Опубликована: Июль 15, 2024

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD), are severe age-related disorders with complex multifactorial causes. Recent research suggests a critical link between neurodegeneration the gut microbiome, via gut–brain communication pathway. This review examines role of trimethylamine N-oxide (TMAO), microbiota-derived metabolite, in development AD PD, investigates its interaction microRNAs (miRNAs) along this bidirectional TMAO, which is produced from dietary metabolites like choline carnitine, has been linked to increased neuroinflammation, protein misfolding, cognitive decline. In AD, elevated TMAO levels associated amyloid-beta tau pathologies, blood–brain barrier disruption, neuronal death. can cross promote aggregation amyloid proteins. Similarly, affects alpha-synuclein conformation aggregation, hallmark PD. also activates pro-inflammatory pathways NF-kB signaling, exacerbating neuroinflammation further. Moreover, modulates expression various miRNAs that involved neurodegenerative processes. Thus, microbiome–miRNA–brain axis represents newly discovered mechanistic dysbiosis neurodegeneration. MiRNAs regulate key oxidative stress, death, contributing progression. As direct consequence, specific miRNA signatures may serve potential biomarkers for early detection monitoring PD aims elucidate interrelationships microbiota, trimethylamine-N-oxide (miRNAs), central nervous system, implications these connections diseases. context, an overview current neuroradiology techniques available studying animal models used investigate intricate pathologies will be provided. summary, bulk evidence supports concept modulating pathway through changes, manipulation and/or miRNA-based therapies offer novel approaches implementing treatment debilitating neurological disorders.

Язык: Английский

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Non-coding RNAs and neuroinflammation: implications for neurological disorders

Experimental Biology and Medicine, Год журнала: 2024, Номер 249

Опубликована: Фев. 28, 2024

Neuroinflammation is considered a balanced inflammatory response important in the intrinsic repair process after injury or infection. Under chronic states of disease, injury, infection, persistent neuroinflammation results heightened presence cytokines, chemokines, and reactive oxygen species that result tissue damage. In CNS, surrounding microglia normally contain macrophages other innate immune cells perform active surveillance. The resulting cytokines produced by these affect growth, development, responsiveness present both white gray matter regions CNS. Controlling levels ultimately improves neurocognitive function lesions associated with neurologic disease. MicroRNAs (miRNAs) are master regulators genome subsequently control activity responses crucial sustaining robust acute immunological towards an infection while dampening pathways chemokines neuroinflammation. Numerous reports have directly implicated miRNAs controlling abundance interleukins, TGF-B, NF-kB, toll-like receptor-signaling intrinsically linked development neurological disorders such as Parkinson’s, ALS, epilepsy, Alzheimer’s, neuromuscular degeneration. This review focused on discussing role play regulating initiating states, many which maintain level and/or neuron-specific secondary messengers. Dysregulated microglia, astrocytes, oligodendrocytes, epididymal cells, contribute to overall glial-specific niche impacts neuronal conductivity, signaling action potentials, neurotransmitter robustness, neuron-neuron specific communication, neuron-muscular connections. Understanding regulate microglial activation step forward developing non-coding RNA-based therapeutics treat potentially correct behavioral cognitive deficits typically found patients suffering from

Язык: Английский

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Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis

Cells, Год журнала: 2024, Номер 13(12), С. 1063 - 1063

Опубликована: Июнь 19, 2024

Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, focus has shifted toward intricate world non-coding RNAs (ncRNAs), class RNA molecules that do not encode proteins but play pivotal roles in gene regulation cellular processes. This review explores emerging significance ncRNAs context neurological disorders, shedding light on diverse functions regulatory mechanisms. The dysregulation various ncRNAs, including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), been implicated pathophysiology conditions such as Alzheimer’s disease, Parkinson’s schizophrenia, mood disorders. delves into specific these modulating key processes, synaptic plasticity, neuroinflammation, apoptosis, providing nuanced impact disease progression. Furthermore, it discusses potential diagnostic therapeutic implications targeting identification ncRNA signatures holds promise for development novel biomarkers early detection, while manipulation expression offers innovative avenues. Challenges future directions field are also considered, highlighting need continued research unravel complexities ncRNA-mediated networks aims provide overview current state knowledge stimulate further exploration fascinating realm brain’s landscape.

Язык: Английский

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