RESUMO
Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. PURPOSE: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. METHODS: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein-protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. RESULTS: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. CONCLUSIONS: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs.
RESUMO
BACKGROUND: To evaluate the reliability of the Soft Tissue Tension Cloud Chart (STTCC) technology, an original method combining multi-point Cervical Paravertebral Soft Tissue Test (CPSTT) with MATLAB software, we conducted a preliminary analysis on the immediate effects of Orthopaedic Manual Therapy (OMT) on cervical paravertebral soft tissue. METHODS: 30 patients with Cervical Spondylotic Radiculopathy (CSR) were included in this study. We analyzed the differences in CPSTT before and after treatment with Cervical Rotation-Traction Manipulation (CRTM), a representative OMT technique in Traditional Chinese Medicine, using the STTCC technology. RESULTS: The STTCC results demonstrated that post-treatment CPSTT levels in CSR patients were significantly lower than pre-treatment levels after application of CRTM, with a statistically significant difference (P < 0.001). Additionally, pre-treatment CPSTT levels on the symptomatic side (with radicular pain or numbness) were higher across the C5 to C7 vertebrae compared to the asymptomatic side (without symptoms) (P < 0.001). However, this difference disappeared after CRTM treatment (P = 0.231). CONCLUSIONS: The STTCC technology represents a reliable method for analyzing the immediate effects of OMT. CSR patients display uneven distribution of CPSTT characterized by higher tension on the symptomatic side. CRTM not only reduces overall cervical soft tissue tension in CSR patients, but can also balance the asymmetrical tension between the symptomatic and asymptomatic sides. TRIAL REGISTRATION: This study was approved by the Chinese Clinical Trials Registry (Website: . https://www.chictr.org.cn .) on 20/04/2021 and the Registration Number is ChiCTR2100045648.