Hydrogen Ion Capturing Hydrogel Microspheres for Reversing Inflammaging

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(5)

Published: Sept. 12, 2023

Inflammaging is deeply involved in aging-related diseases and can be destructive during aging. The maintenance of pH balance the extracellular microenvironment alleviate inflammaging repair tissue damage. In this study, hydrogen ion capturing hydrogel microsphere (GMNP) composed mineralized transforming growth factor-β (TGF-β) catalase (CAT) nanoparticles developed via biomimetic mineralization microfluidic technology for blocking NLRP3 cascade axis inflammaging. This GMNP neutralize acidic by excess ions through calcium carbonate layer. Then, subsequent release encapsulated TGF-β CAT eliminate both endogenous exogenous stimulus NLRP3, thus suppressing excessive activation vitro, suppress TXNIP/NLRP3/IL-1β enhance matrix (ECM) synthesis nucleus pulposus cells. vivo, becomes a sustainable stable niche with microspheres as core to inhibit promote regeneration degenerated intervertebral discs. Therefore, ion-capturing effectively reverses interfering tissues.

Language: Английский

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A mouse coccygeal intervertebral disc degeneration model with tail‐looping constructed using a suturing method

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Backgroud Intervertebral disc degeneration (IDD) is one of the common degenerative diseases. Due to ethical constraints, it difficult obtain sufficient research on humans, so use an animal model IDD very important clarify pathogenesis and treatment mechanism disease. Methods In this study, thirty 2‐month‐old mice were selected for operation establish a coccygeal model. The distal tail portion (beyond 17th vertebra) small piece skin above 8th vertebra excised, two incisions brought together after flexion, secured with sutures. heights signal intensities intervertebral discs (IVDs) assessed using microcomputed tomography (μCT) magnetic resonance imaging (MRI) at 0, 6, 12 weeks postoperatively. overall tissue morphology, cell distribution density, extracellular matrix IVDs also Hematoxylin Eosin (HE), Safranin O‐Fast Green immunohistochemical staining. Results All in experimental group survived operation, there no complications such as wound infection, necrosis suture shedding. results demonstrated that suturing method can successfully initiate IDD. Different severity levels be induced by controlling bending angle within loop; however, consistency, histologic should obtained same looping period. Conclusions This effective studying etiology IVD

Language: Английский

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Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Sept. 10, 2024

Abstract The potent hallucinogen N,N- dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid the Amazonian plant-based brew ayahuasca, which admixture of several β -carboline monoamine oxidase A (MAO-A) inhibitors potentiate activity oral DMT, while possibly contributing other respects complex psychopharmacology ayahuasca. Irrespective route administration, alters perception, mood, cognition, presumably through agonism at serotonin (5-HT) 1A/2A/2C receptors brain, with additional actions receptor types overall effects. Due rapid first pass metabolism, nearly inactive orally, but co-administration -carbolines or synthetic MAO-A (MAOIs) greatly increase bioavailability duration action. synergistic MAOIs ayahuasca formulations may promote neuroplasticity, underlies their promising efficacy clinical trials for neuropsychiatric disorders, including depression, addiction, post-traumatic stress disorder. Advances neuroimaging techniques are elucidating neural correlates DMT-induced altered states consciousness, revealing alterations brain activity, functional connectivity, network dynamics. In this comprehensive narrative review, we present a synthesis current knowledge pharmacology neuroscience -carbolines, should inform future research aiming harness full potential.

Language: Английский

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The Differences on the Fatty Infiltration of Paraspinal Muscles between Single‐ and Multiple‐level Intervertebral Disc Degeneration in Patients with Lumbar Disc Herniation

Orthopaedic Surgery, Journal Year: 2024, Volume and Issue: 16(8), P. 1999 - 2010

Published: July 1, 2024

Objective Multiple‐level Intervertebral disc degeneration (IDD) in patients with lumbar herniation (LDH) is related to postoperative re‐herniation and low back pain. Although many investigators believed that there an interdependence between paraspinal muscles IDD, few studies focused on the fatty infiltration of single‐ multiple‐level IDD LDH. This study aims investigate difference multiple‐levels explore LDH whether a potential risk factor for IDD. Methods was conducted as retrospective observational analysis 82 from January 1, 2020 December 30, our hospital were enrolled. Twenty‐seven cases had single‐level (Group A), 55 B). We measured mean computed tomography (CT) density value muscles, including multifidus (MF), erector spinae (ES) psoas muscle (PM) at each L1 S1. Subgroups set further analyze odds ratio (OR) different sex BMI groups. sagittal angles analyzed relationships these Finally, we use logistic regression, adjusted other confounding factors, independent multi‐level Results The average age (51.40 ± 15.47 years) significantly higher than (33.37 7.10 years). CT MF, ES PM (all p s < 0.001). There no significant two No matter being fat (body mass index [BMI] > 24.0 kg/m 2 ) or normal, MF are easier suffer In pure model, all associated occurrence multi‐IDD. However, after adjusting various only OR remains statistically (OR = 0.810, 0.834, respectively). Conclusions LDH, have more severe those Fatty factors patients.

Language: Английский

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The protective activity of genistein against bone and cartilage diseases

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 8, 2022

Genistein, a natural isoflavone rich in soybean and leguminous plants, has been shown various biological effects, such as anti-inflammation, anti-oxidation, anti-cancer, bone/cartilage protection. Due to the structural similarity estrogen, genistein exhibits estrogen-like activity protecting against osteoporosis osteoarthritis. Furthermore, considered an inhibitor of tyrosine kinase, which found be dysregulated pathological development osteoporosis, osteoarthritis, intervertebral disc degeneration (IDD). Many signaling pathways, MAPK, NF-κB, NRF2/HO-1, are involved regulatory bone cartilage diseases. The potential molecular mechanisms therapeutic management diseases have investigated, but remain fully understood. In this article, we mainly discuss current knowledge diseases, rheumatoid arthritis (RA), IDD.

Language: Английский

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Nucleus Pulposus‐Targeting Nanocarriers Facilitate Mirna‐Based Therapeutics for Intervertebral Disc Degeneration

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(28)

Published: Aug. 25, 2023

Intervertebral disc degeneration (IDD) is a common cause of low back pain. Understanding its molecular mechanisms the basis for developing specific treatment. To demonstrate that miR-22-3p critical in regulation IDD, miRNA microarray analyses are conducted conjunction with vivo and vitro experiments. The knockout (KO) mice show marked decrease histological scores. Bioinformatic analysis reveals plays mechanistic role development IDD by targeting SIRT1, which turn activates JAK1/STAT3 signaling pathway. This confirmed luciferase reporter assay western blot analysis. Therapeutically, delivery inhibitors mimics through synthesized nanoparticles model alleviates aggravates respectively. nanocarriers enhance transportation to nucleus pulposus cells, thus enabling inhibition therapeutic purposes consequently promoting miRNA-specific drugs IDD.

Language: Английский

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MARCHF8-mediated ubiquitination via TGFBI regulates NF-κB dependent inflammatory responses and ECM degradation in intervertebral disc degeneration

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0314021 - e0314021

Published: Jan. 3, 2025

Aim To explore the role of hub gene Transforming Growth Factor Beta Induced (TGFBI) in Intervertebral disc degeneration (IDD) pathogenesis and its regulatory relationship with Membrane Associated Ring-CH-Type Finger 8 (MARCHF8). Background IDD is a prevalent musculoskeletal disorder leading to spinal pathology. Despite ubiquity impact, effective therapeutic strategies remain be explored. Objective Identify key modules associated understand impact TGFBI on nucleus pulposus (NP) cell behavior, extracellular matrix (ECM)-related proteins, Nuclear kappa-light-chain-enhancer Activated B cells (NF-κB) signaling pathway. Methods The GSE146904 dataset underwent Weighted Gene Co-Expression Network Analysis (WGCNA) for module identification Differentially Expressed Genes (DEGs) screening. Intersection analysis, network co-expression identified as gene. In vitro experiments delved into interplay between MARCHF8 their effects NP cells. Results WGCNA linked MEturquoise samples, revealing 145 shared genes among DEGs. findings indicated that determines expression. boosts apoptosis ECM breakdown Lipopolysaccharide-stimulated (LPS-stimulated) Altering levels modulated these NF-κB pathway, influencing inflammatory cytokine concentrations. Moreover, ubiquitination controlled Conclusion TGFBI, by MARCHF8, significantly influences progression affecting apoptosis, degradation, inflammation through

Language: Английский

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Sleep characteristics and intervertebral disc degeneration risk: an observational and Mendelian randomization study

European Spine Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

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HMGB1-mediated macrophage regulation of NF-κB activation and MMP3 upregulation in nucleus pulposus cells: A critical mechanism in the vicious cycle of intervertebral disc degeneration

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111628 - 111628

Published: Jan. 1, 2025

Language: Английский

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Investigation of MicroRNA-17 Expression, Tumor Necrosis Factor-α, and Interleukin-6 Levels in Lumbar Degenerative Disc Disease: Case–Control Study

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(5), P. 1772 - 1772

Published: March 6, 2025

Background/Objectives: The aim of the study is to investigate role microRNA-17 (miRNA-17), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in pathogenesis lumbar degenerative disc disease (LDDD). goal explore how miRNA-17 regulates inflammation apoptosis within intervertebral discs, with a particular focus on its involvement inflammatory pathways via NF-κB signaling. This research seeks uncover molecular mechanisms that contribute LDDD associated chronic lower back pain disability. Methods: A case-control was conducted, involving 110 patients diagnosed 17 healthy control individuals. Serum levels miRNA-17, TNF-α, IL-6 were measured using quantitative real-time PCR enzyme-linked immunosorbent assays (ELISAs). further categorized based severity their condition Oswestry Disability Index (ODI), which classified them into five subgroups. correlation between expression, pro-inflammatory cytokines, analyzed statistically. Results: results demonstrated significant downregulation compared controls. Inflammatory markers TNF-α found be significantly elevated patient group. peak expression observed moderate severe disability (ODI Grade 3), while decreased more advanced stages Grades 4 5), suggesting possible shift dynamics. Conclusions: demonstrates plays regulatory during progression LDDD, particularly through modulation levels. findings indicate most pronounced mid-stages later are characterized by structural damage rather than ongoing inflammation. These insights could help guide future therapeutic strategies aimed at targeting underlying potentially improving outcomes.

Language: Английский

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