BACE1 Aptamer-Modified Tetrahedral Framework Nucleic Acid to Treat Alzheimer’s Disease in an APP-PS1 Animal Model

Alzheimer’s disease is a neurodegenerative disease caused by excessive amyloid β protein-induced neurotoxicity. However, drugs targeting amyloid β protein production face many problems, such as the low utilization rate of drugs by cells and the difficulty of drugs in penetrating the blood–brain barrier. A tetrahedral framework nucleic acid is a new type of nanonucleic acid structure that functions as a therapy and drug carrier. Here, we synthesized a BACE1 aptamer-modified tetrahedral framework nucleic acid and tested its therapeutic effect on Alzheimer’s disease in vitro and in vivo. Our results demonstrated that the tetrahedral framework nucleic acid could be used as a carrier to deliver the BACE1 aptamer to the brain to reduce the production of amyloid β proteins. It also played an antiapoptotic role by reducing the production of reactive oxygen species. Thus, this nanomaterial is a potential drug for Alzheimer’s disease

Forest plot displaying the Risk Difference and 95% CIs of each study for the adequacy rate.

<p>Forest plot displaying the Risk Difference and 95% CIs of each study for the adequacy rate.</p

Operating characteristics in diagnosing pancreatic solid malignant lesions in the two groups (<i>n</i> = 163).

<p>CH-EUS, contrast-enhanced harmonic endoscopic ultrasonography; EUS, endoscopic ultrasonography group; AUC, area under receiver operating characteristic curve; PPV, positive predictive value; NPV, negative predictive value; 95% CI, 95% confidence interval.</p><p>*Suspicious cytology considered as diagnostic of malignancy.</p><p>#Atypical/suspicious cytology considered as a diagnostic of malignancy.</p><p>Operating characteristics in diagnosing pancreatic solid malignant lesions in the two groups (<i>n</i> = 163).</p

Rapid On-Site Evaluation Does Not Improve Endoscopic Ultrasound-Guided Fine Needle Aspiration Adequacy in Pancreatic Masses: A Meta-Analysis and Systematic Review

<div><p>Background and Objectives</p><p>Rapid on-site evaluation (ROSE) during endoscopic ultrasonography-guided fine needle aspiration (EUS–FNA) of pancreatic masses has been reported to be associated with improved adequacy and diagnostic yield. However, recent observational data on the impact of ROSE have reported conflicting results. A meta-analysis and systematic review was therefore conducted to evaluate the contribution of ROSE during EUS-FNA of pancreatic masses.</p><p>Method</p><p>A systematic search was conducted in MEDLINE/Pubmed and EMBASE databases for studies comparing the efficacy of ROSE between patients in two cohorts. Outcomes considered included diagnostic adequate rate, diagnostic yield, number of needle passes, pooled sensitivity and specificity. Findings from a random-effects model were expressed as pooled risk difference (RD) with 95% confidence intervals (CIs).</p><p>Results</p><p>A total of 7 studies (1299 patients) was finally included and further analyzed in the current meta-analysis. EUS-FNA with ROSE could not improve diagnostic adequacy (RD = 0.05, 95% CI: -0.01–0.11) and diagnostic yield (RD = 0.04 95%CI: -0.05, 0.13). The number of needle passes showed no statistically significant difference with and without ROSE (RD = -0.68 95%CI: -2.35, 0.98). The pooled sensitivity and specificity of ROSE group were 0.91 (95%CI: 0.87, 0.94) and 1 (95%CI: 0.94, 1.00). The pooled sensitivity and specificity of non-ROSE group were 0.85 (95%CI: 0.80, 0.89) and 1 (95%CI: 0.95, 1.00). ROSE group and non-ROSE group showed comparable sensitivity and specificity.</p><p>Conclusion</p><p>Compared to historical reports of its clinical efficacy in patients with pancreatic lesions, ROSE may be not associated with an improvement of diagnostic yield, adequate rate, pooled sensitivity and specificity.</p></div

Representative example of a pancreatic neuroendocrine tumor with hyperenhancement.

<p>Conventional endoscopic ultrasonography (left) shows a hypoechoic mass with a clear margin at the pancreas body. Contrast-enhanced harmonic endoscopic ultrasonography (right) indicates that the mass has a hyperenhancement compared to the surrounding tissue.</p

Flow chart of literature search and selection.

<p>Flow chart of literature search and selection.</p

Diagnostic performance for individual studies of meta-analysis comparing EUS-FNA with and without ROSE.

<p>Diagnostic performance for individual studies of meta-analysis comparing EUS-FNA with and without ROSE.</p

Weighted summary receiver operating characteristic (SROC) curve, with 95% confidence interval (CI), for studies involved.

<p><b>a</b> ROSE group; <b>b</b> non-ROSE group.</p

Rapid On-Site Evaluation Does Not Improve Endoscopic Ultrasound-Guided Fine Needle Aspiration Adequacy in Pancreatic Masses: A Meta-Analysis and Systematic Review - Fig 7

<p>Results for the non-ROSE group in individual studies and from pooled data shown as forest plots for: <b>a</b> sensitivity; <b>b</b> specificity. The <i>I</i>² result for heterogeneity is also stated (CI, confidence interval; df, degrees of freedom).</p

Representative example of a pancreatic adenocarcinoma with hypoenhancement.

<p>Conventional endoscopic ultrasonography (left) shows a heterogeneous hypoechoic area without a clear margin at the pancreas head. Contrast-enhanced harmonic endoscopic ultrasonography (right) indicates that most of the area is hypovascular and the remaining area is hypervascular compared to the surrounding tissue. An irregular margin is visible.</p