Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies DOI Creative Commons
Zijun Zhao, Yining Wang, Zairan Wang

et al.

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(11)

Published: Nov. 1, 2024

ABSTRACT Background Intervertebral disc degeneration (IDD) is a major cause for low back pain. Studies showed the association between senescence and degenerative diseases. Cell can promote occurrence development of diseases through multiple mechanisms including inflammatory stress, oxidative stress nutritional deprivation. The roles senescence‐associated genes (SAGs) remains unknown in IDD. Methods Four differently expressed SAGs were identified as hub using “limma“ package R. We then calculated immune infiltration IDD patients, investigated relation infiltration. Enrichment analysis was performed to explore functions Nomogram LASSO model based on constructed predict risk severe (SD) patients. Subsequently, single cell conducted describe expression pattern intervertebral tissue. Results ASPH, CCND1, IGFBP3 SGK1 SAGs. Further demonstrated that might mediate by regulating pathways. four good performance predicting SD. Single revealed CCND1 mainly nucleus pulposus cells, while epithelial cells. Eleven candidate drugs targeting SAGS predicted patients Comparative Toxicogenomics Database (CDT). PCR immunohistochemical levels higher SD than MD (mild degeneration) Conclusions comprehensive IDD, which their Based SAGs, we established predictive explored potential drugs. These findings provide new understandings SAG mechanism promising therapeutic strategies

Language: Английский

Causal Relationship Between Mitochondrial DNA Copy Number and Intervertebral Disc Degeneration: A Bidirectional 2-Sample Mendelian Randomization Study DOI Creative Commons

Chengjie Ma,

Junhua Fang, Rui Xu

et al.

World Neurosurgery, Journal Year: 2025, Volume and Issue: 196, P. 123732 - 123732

Published: March 13, 2025

Language: Английский

Citations

0
Mitochondrial DNA variation and intervertebral disc degeneration: a genotypic analysis in a South African cohort DOI Creative Commons
Megan Collins, Brendon Pearce

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 7, 2025

Non-communicable diseases are multifactorial in that they can be caused by genetic factors, age, sex and poor lifestyle choices. They estimated to account for 71% of deaths globally with 80% these occurring low- middle-income countries. This is particularly true Intervertebral Disc Degeneration associated mitochondrial dysfunction. Interestingly, dysfunction arise from mutations both the nuclear genomes. The present study, therefore, aimed determine if there an association between DNA disc degeneration a South African cohort, addition, generate data understudied populations. Mutations were selected using systematic literature review. was collected buccal swabs extracted standard salt-lysis protocol. Mass-array genotyping done previously reported as well novel mutations. GenAlEx (version 6.5), RStudio SHEsis used statistical analyses. Although no significant associations found, identified polymorphic C16223T, A10398G A8536G found have higher mutant allele frequencies case individuals indicating had larger cohort been used, significance may observed. study able genotypic information Furthermore, identification highlights importance considering future studies cohort.

Language: Английский

Citations

0
Regulating macrophage phenotypes with IL4I1-mimetic nanoparticles in IDD treatment DOI Creative Commons
Jiaying Luo,

Guoxin Jin,

Shaoqian Cui

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 6, 2025

Intervertebral disc degeneration (IDD) is a degenerative spinal condition characterized by structural damage, narrowing of joint spaces, and nerve root compression, significantly reducing patients' quality life. To address this challenge, novel therapeutic strategy was developed using cellulose supramolecular hydrogel as carrier to deliver IL4I1-modified MΦ membrane biomimetic nanoparticles (CHG@IL4I1-MNPs) target tissues. This exhibits excellent biocompatibility mechanical properties while enabling sustained drug release in the microenvironment, enhancing outcomes. CHG@IL4I1-MNPs effectively regulate polarization promoting M2 activation, thereby improving immune microenvironment balance. Animal studies demonstrated that alleviated symptoms IDD, reduced inflammation, supported tissue repair, highlighting its potential reduce reliance on long-term medication improve The uniquely combines nanoparticle technology with immunomodulation, achieving precise targeting MΦs. Beyond approach offers applications other immune-related diseases, providing versatile platform for nanomedicine. study introduces an innovative method treat IDD advances integration immunotherapy nanotechnology, offering both clinical benefits new directions future research. These findings hold strong patient outcomes expanding treatment options related diseases.

Language: Английский

Citations

0
Transcriptome Data Combined With Mendelian Randomization Analysis Identifies Key Genes Associated With Mitochondria and Programmed Cell Death in Intervertebral Disc Degeneration DOI Creative Commons

Hongfei Nie,

Xiao Hu,

Jiaxiao Wang

et al.

JOR Spine, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 1, 2025

ABSTRACT Background Intervertebral disc degeneration (IDD) is a major cause of cervical and lumbar diseases, significantly impacting patients' quality life. Mitochondria cell death have been implicated in IDD, but the key related genes remain unknown. Methods Differentially expressed (DEGs) between IDD control samples were identified using GSE70362. Mitochondria‐related (MRGs) programmed death‐related (PCDRGs) intersected with DEGs to find DE‐MRGs DE‐PCDRGs. Weighted gene co‐expression network analysis (WGCNA) module genes, overlap revealed candidate genes. Mendelian randomization (MR) was used determine causally linked IDD. Machine learning expression validation further refined which then build nomogram predict risk. Additionally, set enrichment (GSEA), immune infiltration, single‐cell performed. Results A total 515 224 yielding 31 Six genes—BCKDHB, BID, TNFAIP6, VRK1, CAB39L, TMTC1—showed causal relationship TMTC1 as through machine validation. developed based on these GSEA BID enriched N‐glycan biosynthesis, TNFAIP6 aminoacyl tRNA ribosomal pathways. Activated dendritic cells, CD56dim natural killer monocytes, other cells elevated strongly correlating activated cells. Key at higher levels degraded samples. Conclusion TMTC1, mitochondria offering new insights for diagnosis treatment.

Language: Английский

Citations

0
Analysis of Nicotine Toxicity and Mechanisms of Senescence in Nucleus Pulposus Cells Using Network Toxicology and Molecular Docking Technique DOI Creative Commons

Chen Jiang,

Chao Song, Chaoqi Chen

et al.

JOR Spine, Journal Year: 2025, Volume and Issue: 8(2)

Published: March 31, 2025

ABSTRACT Aim Through the use of network toxicology, research sought to determine whether cellular senescence and associated molecular mechanisms in nicotine‐induced intervertebral disc degeneration (IVDD) were potentially harmful. Methods The primary chemical structure 105 targets action nicotine determined by using Swiss Target Prediction, Cell Age, PubChem databases. 855 IVDD genes found GEO Age datasets. Results After additional screening Cytoscape development, 9 key identified. Additionally, these targets' co‐expression pattern analysis protein interactions confirmed be identical. core primarily enriched positive regulation cell proliferation, telomere shortening, histone acetylation, senescence‐related processes, according gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG). KEGG signaling pathway also made it clear that Apelin route, nicotinate nicotinamide metabolism, cycle, apoptosis are all strongly linked senescence. We chose four with pathway—HDAC1, HDAC4, NAMPT, MYLK—for docking toxic substance nicotine. findings validated nicotine's strong affinity for targets. Conclusion All things considered, current indicates may contribute via controlling deacetylation process, pathway, pathways metabolism nicotinamide. theoretical foundation investigating is established.

Language: Английский

Citations

0
Strontium alginate hydrogel containing psoralen has superior mechanical properties and immunomodulatory functions to alleviate intervertebral disc degeneration DOI
Jialin Yu, Guofeng Wu,

Z. Liu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142706 - 142706

Published: April 1, 2025

Language: Английский

Citations

0
The BATF2-ATF3 axis exacerbates intervertebral disc degeneration via inducing mitochondrial dysfunction DOI
Cheng Yu, Chun Liu,

Wenhao Kuang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114661 - 114661

Published: April 22, 2025

Language: Английский

Citations

0
HIF-1α protects nucleus pulposus cells from oxidative stress-induced mitochondrial impairment through PDK-1 DOI Creative Commons
Zhuochao Liu, Jiancheng Zheng, Tao Ding

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 224, P. 39 - 49

Published: Aug. 10, 2024

The pathogenesis of intervertebral disc degeneration (IVDD) involves complex signaling networks and various effector molecules, our understanding the IVDD is limited. Hypoxia inducible factor-1α (HIF-1α) closely related to IVDD, there excessive oxidative stress concurrent with IVDD. In this study, we found that HIF-1α could protect nucleus pulposus cells from by reversing imbalance between oxidants antioxidants thus mitigating stress-induced mitochondrial impairment. With further exploration, pyruvate dehydrogenase kinase 1 (PDK-1) was involved in protective effect on under stress. We suggested preserve integrity activate glycolysis via PDK-1, addition DCA, a PDK-1 inhibitor, blunt HIF-1α. addition, HIF-1α/PDK-1 regulatory axis also confirmed vivo through knockout mice model. Therefore, propose protects maintaining enriching insight into mechanism against providing novel therapeutic target for treatment

Language: Английский

Citations

3
Antioxidant activities of metal single-atom nanozymes in biomedicine DOI
Qingdong Zeng, Huihai Zhong, Jiahao Liao

et al.

Biomaterials Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Nanozymes are a class of nanomaterials with enzyme-like activity that can mimic the catalytic properties natural enzymes. The small size, high activity, and strong stability nanozymes compared to those enzymes allow them not only exist in wide temperature pH range but also maintain complex environments. Recently developed single-atom have metal active sites composed single atom fixed carrier. These atoms act as independent catalytically centers. Metal homogeneous structure suitable coordination environment for stronger specificity than traditional nanozymes. antioxidant ability removing reactive oxygen species (ROS) simulate superoxidase dismutase, catalase, glutathione peroxidase show different effects

Language: Английский

Citations

3
Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration DOI

Jiawen Zhan,

Yongzhi Cui, Ping Zhang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(2)

Published: Nov. 18, 2024

Abstract Cartilage endplate cell (CEPC) and nucleus pulposus (NPC) inflammation are critical factors that contribute to intervertebral disc degeneration (IVDD). Recent evidence indicated iron ion influx, reactive oxygen species (ROS), the cGAS‐STING pathway involved in CEPC inflammatory degeneration. Moreover, cytokines produced by degenerating CEPCs lactic acid accumulation within microenvironment significantly NPC inflammation. Consequently, simultaneous alleviation of correction acidic anticipated reverse IVDD. Herein, CEPC‐targeted engineered exosomes loaded with salvianolic A incorporated into a CaCO 3 /chitosan hydrogel, forming composite gel, CAP‐sEXOs@Gel. Notably, CAP‐sEXOs@Gel shows long local retention, realizes slow release CAP‐sEXOs specific uptake CEPCs. After CEPCs, reduce intracellular ROS inhibiting hypoxia‐inducible factor‐2α (HIF‐2α)/TfR1 expression. Iron influx inhibition maintenance normal mitochondrial function reduced mtDNA leakage, suppresing pathway. Additionally, component neutralizes H + , thereby alleviating Collectively, this novel hydrogel demonstrates ability concurrently inhibit inflammation, presenting promising therapeutic approach for

Language: Английский

Citations

3