The connection between 91 inflammatory cytokines and frailty mediated by 1400 metabolites: An exploratory two-step Mendelian randomization analysis

Archives of Gerontology and Geriatrics, Год журнала: 2025, Номер 133, С. 105774 - 105774

Опубликована: Фев. 25, 2025

Язык: Английский

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The causal relationship between circulating inflammatory proteins and heart failure: A two-sample Mendelian randomization study

Medicine, Год журнала: 2025, Номер 104(1), С. e41115 - e41115

Опубликована: Янв. 3, 2025

This study aims to explore the causal associations of 91 circulating inflammatory proteins with ischemic cardiomyopathy heart failure (ICM), dilated (DCM), and hypertrophic (HCM) provide new ideas for relevant mechanisms, adjunctive diagnosis differentiation, clinical application drug targets. An analysis relationship between was conducted via inverse-variance weighted, weighted median estimator (WME), mode (WM), Mendelian randomization-Egger regression randomization. A randomization revealed that natural killer cell receptor 2B4 levels, CXCL-6, fibroblast growth factor 5 interleukin-10 levels had positive relationships ICM, whereas CX3CL-1, C-X-C motif chemokine 9 leukemia inhibitory signaling lymphocytic activation molecule negative relationships; C-C 20 oncostatin-M were positively correlated DCM, eukaryotic translation initiation 4E-binding protein 1 Fms-related tyrosine kinase 3 ligand negatively associated DCM; CD40L receptor, hepatocyte sulfotransferase 1A1 HCM. In this study, causally related ICM (4 positive, negative), 7 DCM (5 2 4 HCM (all negative). provides a theoretical foundation mechanisms failure, diagnosis, treatment, as well potential candidates closely failure.

Язык: Английский

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Exploring the mediating role of cerebrospinal fluid metabolites in the pathway from circulating inflammatory proteins to multiple sclerosis: A Mendelian randomization study

Multiple Sclerosis and Related Disorders, Год журнала: 2025, Номер unknown, С. 106440 - 106440

Опубликована: Апрель 1, 2025

Язык: Английский

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The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial

BMC Pharmacology and Toxicology, Год журнала: 2025, Номер 26(1)

Опубликована: Май 12, 2025

Abstract Background Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated aerosol inhalation of IFNα is both effective safe for treating respiratory infections. However, has a short half-life rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation common strategy to extend duration drug action. PegIFNα-2b long-acting interferon formed covalent binding 40 kDa Y-shaped branched PEG with recombinant human IFNα-2b. This study aimed assess safety, tolerability, pharmacokinetic, pharmacodynamic characteristics nebulized in healthy adult subjects, providing guidance further clinical investigations. Methods employed randomized, controlled trial design total 18 subjects enrolled. Participants were randomly assigned 1:1:1 ratio three groups. Treatment group 1 2 received 90 µg 180 PegIFNα-2b, respectively, while control was administered combination 15 mg inhalable Ambroxol Hydrochloride solution, all single dose. Safety, blood concentration assessed, along neopterin levels pharmacokinetic evaluation. Results The incidence adverse events (AEs) 38.9% (7/18) no significant difference among groups ( P > 0.05). AEs included anemia N = 5) leukopenia 2), predominantly grade severity (6/7), severe events. Blood concentrations below detection limits most except one treatment 2. Neopterin generally low group, slightly higher observed 2, but differences not Conclusions Nebulized at doses showed acceptable safety tolerability. Minimal systemic absorption following inhalation. Further studies needed explore its potential, especially patients lower tract Clinical registration ChiCTR2300074909, retrospectively registered https://www.chictr.org.cn/ 20 August 2023.

Язык: Английский

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Causal association between circulating inflammatory proteins and peripheral artery disease: a bidirectional two-sample Mendelian randomization study

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 16, 2024

Introduction A growing body of research has shown a strong connection between circulating inflammatory proteins and Peripheral artery disease (PAD). However, the causal relationship PAD is still not fully understood. To investigate this association, we conducted bidirectional Mendelian randomization study. Materials methods Our study utilized genetic variation data obtained from genome-wide association studies (GWAS) datasets. Specifically, GWAS dataset related to (identifier: finn-b-I9_PAD) included 7,098 cases 206,541 controls. Additionally, extracted on 91 another (identifiers: GCST90274758-GCST90274848), involving 14,824 participants. assess development, employed methodologies such as inverse variance weighting (IVW), MR Egger regression, weighted median approach. Furthermore, sensitivity analyses were ensure reliability robustness our findings. Results Two found be significantly associated with risk: Natural killer cell receptor 2B4 levels (OR, 1.219; 95% CI,1.019~1.457; P=0.03), Fractalkine 0.755; CI=0.591~0.965; P=0.025). had statistically significant effects 12 proteins: C-C motif chemokine 19 0.714; CI, 0.585 0.872; P=0.001), T-cell surface glycoprotein CD5 0.818; 0.713 0.938; P=0.004), CUB domain-containing protein 1 0.889; 0.809 0.977; P=0.015), Fibroblast growth factor 23 1.129; 1.009 1.264; P=0.034), Interferon gamma 1.124; (1.011 1.250); P=0.031),Interleukin-15 subunit alpha 1.183; CI,(1.005 1.392); P=0.044), Interleukin-17C (OR,1.186; (1.048 1.342); P=0.007), Interleukin-1-alpha 1.349; (1.032 1.765); P=0.029), Interleukin-5 1.119; CI,(1.003 1.248); P=0.043), Latency-associated peptide transforming beta (OR,1.123; (1.020 1.236); P=0.018), Matrix metalloproteinase-10 CI,(1.015 1.233); P=0.024), Signaling lymphocytic activation molecule 0.823; (0.693 0.978); P=0.027). Conclusion expands exploring PAD. This discovery potential inform shape future clinical basic endeavors in area.

Язык: Английский

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Association of eczema with risk of pan-cancers: a two-sample Mendelian randomization study

Oncology and Translational Medicine, Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Abstract Background Both eczema and tumor are associated with immune disorders. Although several investigations have observed the relationship between certain cancers, evidence for causality is lacking. Methods We conducted a two-sample Mendelian randomization (MR) study to examine explore genetic association pan-cancers. Upon satisfying three core assumptions of MR, we analyzed 15 site-specific cancers utilizing an inverse variance weighted method. verified results through series sensitivity reverse direction analyses. The exposure outcome datasets were substituted from FinnGen genome-wide studies catalog databases. A meta-analysis on primary validation analyses was performed combine estimates MR study. Results Based analysis results, increased risk lung cancer (odds ratio [OR] = 1.0427, 95% confidence interval [CI] 1.0082–1.0783, P 0.0148) brain (OR 1.0285, CI 1.0120–1.0452, 0.0007) decreased colorectal 0.9324, 0.8774–0.9909, 0.0242) malignant neoplasm kidney 0.9323, 0.8834–0.9839, 0.0108). indicated that stable reliable, demonstrated no causation interest eczema. Conclusions Our identified as factor protective kidney. No connection other cancers. Further epidemiological mechanistic needed elucidate these findings in detail.

Язык: Английский

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Genetic prediction of serum micronutrient levels and the risk of frailty: Evidence from a Mendelian randomization study

Medicine, Год журнала: 2024, Номер 103(51), С. e40874 - e40874

Опубликована: Дек. 20, 2024

Although observational studies have revealed a link between frailty and serum micronutrient levels, it remains unclear whether these 2 states are directly connected. Thus, Mendelian randomization (MR) was used to investigate the causal relationship blood levels. Summary-level data for 15 micronutrients (copper, selenium, zinc, calcium, iron, magnesium, potassium, folate, carotene, vitamin A, B6, B12, C, D, E) were obtained from people of European ancestry Integrative Epidemiology Unit. Single nucleotide polymorphisms associated with index extracted published meta-analysis study in UK Biobank Swedish TwinGene. We inverse variance weighted (IVW) method primary analysis. employed pleiotropy residual sum outlier (MR-PRESSO) tests, MR-Egger intercepts, Cochran Q leave-one-out analysis assess causality validity robustness. Reverse MR determine reverse causation. The IVW results that D (odds ratio [OR] = 1.096; 95% confidence interval [CI]: 1.019–1.178; P .014) increased likelihood high risk frailty, whereas had protective effect on selenium (OR 0.622; CI: 0.396–0.977; .039), carotene 0.916; 0.858–0.979; .009), C 0.895; 0.837–0.957; .001), iron 0.921; 0.859–0.988; .022), E 0.907; 0.847–0.971; .005). no significant correlation levels indices. links frailty. Notably, our findings highlight necessity adjuvant management.

Язык: Английский

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Inflammatory proteins and vestibular neuronitis: A Mendelian randomization study

Medicine, Год журнала: 2024, Номер 103(51), С. e41081 - e41081

Опубликована: Дек. 20, 2024

Previous studies have highlighted the correlation between inflammatory responses and vestibular neuritis (VN). The aim of Mendelian randomization was to assess causal associations 91 proteins comprehensively. By leveraging publicly accessible genetic datasets, we probed whether serve as upstream determinants neuritis. We conducted a comprehensive sensitivity analysis robustness, heterogeneity, polygenicity our findings. Three were found exert significant effect on VN: eotaxin levels are associated with reduced risk VN (inverse variance weighting [IVW]: odds ratio [OR] = 0.7113, 95% confidence intervals [CI] 0.5199–0.9731, P .0331). Similarly, measurement monocyte chemotactic protein-2 is linked decreased (IVW: OR 0.8535, CI 0.7328–0.9942, .0418). Conversely, an increase in level T-cell surface glycoprotein CD5 correlated increased 1.3969, 1.0095–1.9331, .0437). This study suggested that eotaxin, protein-2, may play crucial roles pathogenesis VN. potential use these for diagnosing or therapeutic targets has clinical implications.

Язык: Английский

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