Mendelian randomization analysis to identify potential drug targets for osteoarthritis

PLoS ONE, Год журнала: 2025, Номер 20(2), С. e0316824 - e0316824

Опубликована: Фев. 11, 2025

Background Osteoarthritis (OA) is a prevalent chronic joint disease for which there lack of effective treatments. In this study, we used Mendelian randomization analysis to identify circulating proteins that are causally associated with OA-related traits, providing important insights into potential drug targets OA. Method Causal associations between 1553 and five traits were assessed in large-scale two-sample MR analyses using Wald ratio or inverse variance weighting, the results corrected Bonferroni. addition, sensitivity performed validate reliability results, including reverse Steiger filtering ensure causal direction OA; Bayesian co-localization phenotypic scanning eliminate confounding effects horizontal pleiotropy. External validation was exclude incidental findings novel plasma protein quantitative trait loci. Finally, online tool Enrichr utilized screen drugs molecular docking predict binding modes energies most stable likely drugs. Result Four ultimately found be reliably three features: DNAJB12 USP8 knee OA, IL12B spinal RGMB thumb The ORs above 1.51 (95% CI, 1.26–1.81), 1.72 1.42–2.08), 0.87 0.81–0.92), 0.59 0.47–0.75), respectively. Drug-predicting small molecules (doxazosin, XEN 103, montelukast) simultaneously target proteins, DNAJB12, USP8, IL12B, docked well. Conclusion Based on our comprehensive analysis, can draw conclusion relationship genetic levels , risk respective OA.They may options OA screening prevention clinical practice. They also serve as candidate future mechanism exploration selection.

Язык: Английский

Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6–36 months after COVID-19

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 5, 2025

Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis acute COVID-19, long-term molecular changes in COVID-19 convalescents with remain poorly understood. We prospectively recruited 70 who had been diagnosed from 7 January 2020 29 May (i.e., convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), physical examination center before pandemic, served comparison group. explored proteomic metabolomic profiles 174 plasma samples 35 CONs. comprehensive analysis investigate host up Our multi-omics revealed activation cytoskeletal organization glycolysis/gluconeogenesis, well suppression gas transport adaptive immune responses, convalescents. Additionally, metabolites involved glutathione metabolism; alanine, aspartate, glutamate ascorbate aldarate metabolism were significantly upregulated Pulmonary abnormalities persisted convalescents; impaired (DLco) was most prominent feature. used this profile develop model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) two (arachidonoyl-EA 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) identification abnormal DLco. These data provide insights concerning among discharge, clarify mechanisms driving sequelae, support development novel predict This longitudinal may illuminate trajectory altered lung function

Язык: Английский

Plasma Proteomic Profiles of Pediatric Patients With Human Herpesvirus 6B Encephalitis Following Umbilical Cord Blood Transplantation

Journal of Medical Virology, Год журнала: 2025, Номер 97(3)

Опубликована: Март 1, 2025

ABSTRACT Human herpesvirus 6B (HHV‐6B) encephalitis is a rare but severe complication of hematopoietic cell transplantation. This study investigated the pathogenesis HHV‐6B by comparing plasma proteomic profiles four pediatric patients with to three asymptomatic reactivation following umbilical cord blood transplantation (UCBT). Plasma profiling was conducted using liquid chromatography‐mass spectrometry. Overall, 260 proteins were identified and quantified in samples. At onset reactivation, 20 24 proteins, respectively, significantly upregulated compared their respective pre‐onset levels. Of these, 11 uniquely encephalitis. S100‐A9 S100‐A8 most second‐most encephalitis, respectively. Elevated S100A8/A9 heterodimer levels confirmed via enzyme‐linked immunosorbent assay Pathway analysis neutrophil degranulation as enriched category among Additionally, related protein‐lipid complex remodeling pathway more prominently than reactivation. Proteomic revealed distinct protein between UCBT recipients. The inflammatory response mediated may play critical role These findings indicate that provide novel insights into host subsequent development

Язык: Английский