New mechanism and early warning based on LASS2 gene-mediated renal cancer progression for preparing drugs for treating or diagnosing renal cancer, involves comprises searching Human Protein Atlas database, performing western blot detection, and constructing LASS2 knockdown/overexpression plasmid
基于LASS2基因介导的肾癌进展的新机制和预警，用于制备治疗或诊断肾癌的药物，包括搜索人类蛋白质图谱数据库、进行蛋白质印迹检测和构建LASS2敲低/过表达质粒
摘要 (Abstract)
<jats:sec> <jats:title>Objective</jats:title> <jats:p>To investigate the association between serum complement component 3 (C3) levels and renal pathological injury across different estimated glomerular filtration rate (eGFR) strata in patients with diabetic kidney disease (DKD) and evaluate its potential as an early-warning biomarker.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This retrospective study enrolled 187 DKD patients. Serum C3 levels were measured, and renal biopsies were evaluated by two independent pathologists using a standardized scoring system. Patients were stratified by eGFR (low: &lt;90; high: ≥90 ml/min/1.73m²). The association between serum C3 levels and renal injury was evaluated using multivariable linear regression and binary logistic regression analyses, after adjusting for age, sex, TC, duration of diabetes, HbA1c, albumin and 24-h (24-hour) proteinuria. Restricted cubic spline analysis explored nonlinear relationships in the low eGFR subgroup. Exploratory longitudinal analysis was performed to compare changes in 24-h proteinuria over 1 year of follow-up between patients stratified by serum C3 levels.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> Serum C3 levels were negatively correlated with renal C3 deposition and eGFR (ρ = −0.167, <jats:italic>P</jats:italic> = 0.022; ρ = 0.238, <jats:italic>P</jats:italic> = 0.001). In patients with low eGFR, lower C3 levels were consistently associated with higher renal pathology (RP) scoring. After full adjustment, this association remained significant (β = −2.640, <jats:italic>P</jats:italic> = 0.047). Interstitial fibrosis and tubular atrophy and C3 (OR = 0.09, <jats:italic>P</jats:italic> = 0.037), showed significant inverse associations. Restricted cubic spline analysis demonstrated a linear relationship ( <jats:italic>P</jats:italic> for overall = 0.031, <jats:italic>P</jats:italic> for nonlinear = 0.079). At 1-year follow-up, exploratory longitudinal analysis showed that patients with lower C3 (&lt;1.10 g/L) showed significantly greater 24-h proteinuria progression (-2869.27 vs. 250.46 mg/24h, <jats:italic>P</jats:italic> = 0.040). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In DKD patients with eGFR &lt;90 ml/min/1.73m², reduced serum C3 levels are associated with specific renal pathological injuries and may serve as a biomarker of disease progression.</jats:p> </jats:sec>
实验设计与方法 (Experimental Design & Methods)
采用结构生物学、计算机模拟和实验验证相结合的方法，系统分析蛋白质结构和功能关系。通过分子对接、动力学模拟等技术预测药物-靶点相互作用。
实验结果 (Experimental Results)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
数据汇总 (Data Summary)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
结论 (Conclusions)
基于蛋白质的药物研发策略为创新药物开发提供了新方向。
实践意义 (Practical Significance)
对推动靶向药物研发和精准医疗发展具有重要科学价值。