Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using an interpretable machine learning framework: a UK biobank study DOI Creative Commons
Ramneek Gupta, Rikke Linnemann Nielsen, Thomas Monfeuga

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Авг. 10, 2023

Abstract Osteoarthritis (OA) is increasing in prevalence and has a severe impact on patients’ lives. However, our understanding of biomarkers driving OA risk remains limited. We developed model predicting the five-year OA, integrating clinical, lifestyle biomarker data from UK Biobank (19,120 patients with ROC-AUC:0.72 95%CI (0.71 – 0.73)). Higher age, BMI, prescription non-steroidal anti-inflammatory drugs contributed most to increased prediction. 14 sub-groups profiles were identified, validated an independent set evaluating 11-year risk, 88% uniquely assigned one sub-groups. Individual characterised by personalised biomarkers. Omics integration demonstrated predictive importance key genes pathways (e.g. GDF5 TGF-β signalling) identified OA-specific CRTAC1 COL9A1). In summary, this work opportunities for prevention insights into its underlying pathogenesis.

Язык: Английский

Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using interpretable machine learning DOI Creative Commons
Rikke Linnemann Nielsen, Thomas Monfeuga, Robert R. Kitchen

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 1, 2024

Abstract Osteoarthritis (OA) is increasing in prevalence and has a severe impact on patients’ lives. However, our understanding of biomarkers driving OA risk remains limited. We developed model predicting the five-year diagnosis, integrating retrospective clinical, lifestyle biomarker data from UK Biobank (19,120 patients with OA, ROC-AUC: 0.72, 95%CI (0.71–0.73)). Higher age, BMI prescription non-steroidal anti-inflammatory drugs contributed most to increased prediction ahead diagnosis. identified 14 subgroups profiles. These were validated an independent set evaluating 11-year risk, 88% being uniquely assigned one subgroups. Individual profiles characterised by personalised biomarkers. Omics integration demonstrated predictive importance key genes pathways (e.g., GDF5 TGF-β signalling) OA-specific CRTAC1 COL9A1). In summary, this work identifies opportunities for prevention insights into its underlying pathogenesis.

Язык: Английский

Процитировано

19

Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis DOI Creative Commons
Zeyu Han, Ketao Wang, Shenglong Ding

и другие.

Bone Research, Год журнала: 2024, Номер 12(1)

Опубликована: Дек. 3, 2024

Abstract Osteoarthritis (OA) poses a significant challenge in orthopedics. Inflammatory pathways are regarded as central mechanisms the onset and progression of OA. Growing evidence suggests that senescence acts mediator inflammation-induced Given lack effective treatments for OA, there is an urgent need clearer understanding its pathogenesis. In this review, we systematically summarize cross-talk between cellular inflammation We begin by focusing on hallmarks senescence, summarizing supports relationship inflammation. then discuss interaction inflammation, including senescence-associated secretory phenotypes (SASP) effects pro- anti-inflammatory interventions senescence. Additionally, focus various types cartilage, subchondral bone, synovium, infrapatellar fat pad, stem cells, immune elucidating their impacts Finally, highlight potential therapies targeting senescent cells OA strategy promoting cartilage regeneration.

Язык: Английский

Процитировано

13

In-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level DOI Creative Commons
Shaojie Qin, Y. Victoria Zhang,

Mingying Shi

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 23, 2024

Abstract Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. However, metabolomics remains challenging because of limited metabolite coverage inability to discriminate isomers. Herein, we establish a platform in-depth organic mass cytometry. Extended analysis time guarantees sufficient MS/MS acquisition identification isomers discrimination while online sampling ensures high-throughput method. The largest number identified metabolites (approximately 600) are achieved in single cells fine subtyping MCF-7 first demonstrated by an investigation on differential levels 3-hydroxybutanoic acid among clusters. Single-cell transcriptome reveals differences expression downstream antioxidative stress genes, such as metallothionein 2 (MT2A), fluorescence-activated cell sorting assay confirms positive relationship between target proteins; these results suggest that provides cancer with different ability resist surrounding oxidative stress. Our method paves way deep metabolome investigations physiological pathological processes occur during cancer.

Язык: Английский

Процитировано

7

Specific gut microbiota and serum metabolite changes in patients with osteoarthritis DOI Creative Commons
Wendong Wang, Xincheng Liu, Nan Hao

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 14, 2025

Introduction Recent research indicated a strong link between the gut microbiota and osteoarthritis. However, complex interplay microbiota, serum metabolites, progression of osteoarthritis in affected individuals remains largely unexplored. This study aimed to investigate characteristics metabolites patients with Methods Participants either healthy knees or were enrolled categorized into control (HC) (OA) groups. Fecal blood samples collected for 16S rRNA gene sequencing, metabolomic analysis via liquid chromatography–mass spectrometry (LC-MS), integrated evaluation. Results The results showed no significant variation richness diversity two abundance Bacteroides plebeius Faecalibacterium prausnitzii was reduced OA group, both which are known their potential as next-generation probiotics human health. Metabolomic that including pyrogallol 3-hydroxybutyrate (3HB), significantly lower group. These positively impact other diseases demonstrated good diagnostic performance distinguishing from controls. Correlation revealed positive correlation 3HB. Discussion highlighted specific metabolite profiles patients, suggesting changes bacteria derived closely tied progression. underscores modifiable elements therapeutic targets prevention.

Язык: Английский

Процитировано

1

Modulation of gut microbiota by crude mulberry polysaccharide attenuates knee osteoarthritis progression in rats DOI
Yizhou Zheng,

Qing-Rou Chen,

Hongmei Yang

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 262, С. 129936 - 129936

Опубликована: Фев. 1, 2024

Язык: Английский

Процитировано

4

The anti-senescence effect of D-β-hydroxybutyrate in Hutchinson-Gilford progeria syndrome involves progerin clearance by the activation of the AMPK-mTOR-autophagy pathway DOI Creative Commons
Feliciano Monterrubio-Ledezma,

Ashley Salcido-Gómez,

Tania Zavaleta-Vásquez

и другие.

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

D-β-hydroxybutyrate, BHB, has been previously proposed as an anti-senescent agent in vitro and vivo several tissues including vascular smooth muscle. Moreover, BHB derivatives ketone esters alleviate heart failure. Here, we provide evidence of the potential therapeutic effect on Hutchinson-Gilford progeria syndrome (HGPS), a rare condition characterized by premature aging failure, caused presence progerin, aberrant protein derived from LMNA/C gene c.1824C > T mutation. We have assessed hallmarks HGPS-senescent phenotype vitro, such progerin levels, nuclear morphometric aberrations, nucleolar expansion, cellular senescent morphology, SA-βGal-positive cells, H3K9me3 heterochromatin, γH2AX foci, Lamin B1, p21Waf1/Cip1 p16CDKN2A abundance, autophagy. Strikingly, improved morphometrics, diminished senescence-phenotype, unstuck autophagy HGPS observed enhanced degradation cargo receptor SQSTM1/p62, suggesting stimulation autophagic flux. Additionally, decrease cause senescence HGPS. Furthermore, compound C, inhibitor AMPK, SBI-0206965, ULK1/2 which prevent activation, reversed BHB-induced decline well its AMPK-mTORC1 dependent manner. Altogether, these results suggest that anti-senescence involves clearance activation supporting for therapeutics further preclinical trials.

Язык: Английский

Процитировано

0

A multidimensional approach reveals the function of lactylation related genes in osteoarthritis DOI Creative Commons
Shanjie Luan,

Jian Luan

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 5, 2025

As a complex joint disease, osteoarthritis (OA) increasingly affects the elderly. Currently, existing drugs cannot cure OA. There is an urgent need for new targets. Lactylation closely related to inflammation and emerging target in treatment. However, potential of lactylation-related genes (LRGs) OA poorly understood. This study identified differentially expressed (DELRGs) through bioinformatics analysis, constructed model combination various machine learning methods, performed immune infiltration single-cell analysis molecular docking predict drugs. Mendelian randomization was used causal relationships between eQTLs three types osteoarthritis. Finally, we RT-qPCR CCK-8 assays validate results analysis. We generated with good diagnostic efficacy seven hub genes, which revealed that associated cells such as dendritic macrophages, well cell communication fibroblasts macrophages. Azacitidine, significant results, obtained genes. The verified expression LRGs assay indicated azacitidine can significantly inhibit proliferation cells. Overall, established lactylation-based novel biomarkers, are expected lead development strategies diagnosis treatment

Язык: Английский

Процитировано

0

New insights into the role of cellular senescence and rheumatic diseases DOI Creative Commons
Jianting Wen, Jian Li, Lei Wan

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 16, 2025

Rheumatic disease is a chronic inflammatory that imposes significant societal and economic burdens. Accumulating evidence has demonstrated cellular senescence plays an important role in inflammation-induced rheumatic diseases. Due to the lack of effective therapies, there urgent need for deeper understanding etiopathogenesis In this review, we systematically summarized We first focused on mechanisms hallmarks senescence, then can induce or aggravate as well related signaling pathways. Next, discussed interaction between Additionally, elucidated impacts chondrocyte mesenchymal stem cell (MSC) osteoarthritis (OA) systemic lupus erythematosus (SLE), respectively. Finally, highlighted potential therapies targeting senescent cells diseases strategy, especially multi-target effect traditional Chinese medicine.

Язык: Английский

Процитировано

0

LncRNA linc00641 Inhibits the Proliferation and Differentiation of Chondrocytes and Aggravates Joint Injury by Targeting miR-320a DOI

Stella Han,

Huiping Liu, Yu Wang

и другие.

Russian Journal of Genetics, Год журнала: 2024, Номер 60(10), С. 1417 - 1426

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

0

Primary components of MCT ketogenic diet are detrimental to bone loss associated with accelerated aging and age-related neurotoxicity in mice DOI
Shreshta Jain, Divya Vohora

Bone, Год журнала: 2024, Номер unknown, С. 117383 - 117383

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

0