Causal Associations of Inflammatory Cytokines With Osteosarcopenia: Insights From Mendelian Randomization and Single Cell Analysis

Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Osteosarcopenia, the coexistence of osteoporosis and sarcopenia, poses significant challenges in aging populations due to its dual impact on bone muscle health. Inflammation, mediated by specific cytokines, is thought play a crucial role development osteosarcopenia, though underlying mechanisms are not fully understood. Objective: This study aimed clarify causal circulating cytokines pathogenesis osteosarcopenia employing mendelian randomization (MR) single-cell RNA sequencing (scRNA-seq) identify cell-specific cytokine expression patterns. The ultimate objective was uncover potential pathological therapeutic targets for treating osteosarcopenia. Methods: A two-sample MR approach employed, leveraging publicly available genome-wide association (GWAS) data from multiple cohorts. total 91 were examined using genetic instruments, their effects traits related sarcopenia evaluated. Various complementary sensitivity analyses performed ensure robust findings. Additionally, scRNA-seq datasets human marrow analyzed validate profiles candidate cytokines. Results: analysis identified several with traits, including LTA, CD40, CXCL6, CXCL10, DNER (delta notch-like epidermal growth factor-related receptor), VEGFA (vascular endothelial factor A). LTA CD40 protective both muscle, while posed risk. Other demonstrated opposite muscle. Single cell revealed distinct patterns, highly expressed lymphocytes, immune cells, various musculoskeletal types. Age-related differences also noted, more younger individuals, older individuals. Conclusion: offers preliminary insights into inflammatory potentially driving identifying key that may be involved pathogenesis. By integrating data, we highlight targets, further research needed confirm these findings implications

Language: Английский

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Effect of abdominal tissue thickness on trabecular bone score and fracture risk in adults with diabetes: the Manitoba BMD registry

Journal of Bone and Mineral Research, Journal Year: 2024, Volume and Issue: 39(7), P. 877 - 884

Published: May 13, 2024

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher mineral density. However, measures of microarchitecture from high-resolution peripheral computed tomography are not in diabetes. We hypothesized that confounding effects abdominal tissue thickness may explain this discrepancy, since central obesity is a factor for also artifactually lowers TBS. This hypothesis was tested individuals aged 40 years older large DXA registry, stratified by sex status. When DXA-measured included as covariate, men without had TBS than women (mean difference -0.074, P < .001). versus -0.037, .001), -0.007, = .042). adjusted these findings reversed, became greater +0.053, +0.008, +0.014, During mean 8.7 observation, incident major osteoporotic fractures were seen 7048 (9.6%). Adjusted multiple covariates except thickness, predicted all subgroups no significant interaction. further HR per SD remained even slightly. In conclusion, predicts independent other clinical factors both men, Excess using the current algorithm, which reverses after accounting thickness. supports ongoing efforts to update algorithm directly account improved prediction.

Language: Английский

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Impact of 26 Skin Diseases on the Risk of Non-Small Cell Lung Cancer: A Mendelian Randomization Study Using FinnGen R11 Data

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Abstract Purpose To determine whether genetic predisposition to various skin diseases influences the risk of non-small cell lung cancer (NSCLC) through Mendelian randomization (MR). Methods Single nucleotide polymorphisms (SNPs) associated with 26 were extracted from FinnGen R11 dataset and underwent rigorous quality control. evaluate association between these (NSCLC), we applied several analytical methods, including inverse-variance weighted (IVW), MR-Egger regression, median, Simple mode, Weighted mode. The robustness findings was further supported by assessing SNP heterogeneity Cochran Q test evaluating horizontal pleiotropy using intercept test. Results Our study revealed that genetically predicted dermatitis herpetiformis (DH) significantly an elevated squamous carcinoma (SCC). Acne nominally linked increased SCC. Additionally, rhinophyma (RHN), hidradenitis suppurativa (HS), DH a higher adenocarcinoma (ADC). Of remaining 22 analyzed, 7 lacked sufficient instrumental variables meet inclusion criteria. other 15 showed no statistically significant NSCLC. Conclusion This ultimately analyzed relationship 19 NSCLC at level, while could not be due insufficient variables. Dermatitis acne lung. rhinophyma, suppurativa,

Language: Английский

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