The sonic hedgehog (SHH) signaling pathway exhibits aberrant activation in triple-negative breast cancer (TNBC), wherein it regulates several malignant phenotypes related to tumor metastasis. GANT61, an inhibitor of the SHH signaling pathway, may offer promise when administered in combination with conventional chemotherapy to treat metastatic TNBC. However, poor bioavailability and substantial off-target toxicity limit its clinical application. To address these limitations, we designed a peptide-functionalized dual-targeting delivery system encapsulating paclitaxel and GANT61 in tLyP-1 peptide-modified reconstituted high-density lipoprotein nanoparticle (tLyP-1-rHDL-PTX/GANT61 NP) for metastatic TNBC treatment. The apolipoprotein A-1 and tLyP-1 peptide modified on the surface of nanoparticles enable the delivery system to target tumor cells by binding to the overexpressed scavenger receptor B type I and neuropilin-1 receptor. Moreover, the tLyP-1 peptide also enables the deep tumor penetration of nanoparticles further facilitating paclitaxel and GANT61 delivery. Increased cellular uptake of the nanoparticles was observed in both MDA-MB-231, BT-549 tumor cells, and their 3D tumor spheroids. A series of in vitro experiments reveal that GANT61 was able to suppress key metastasis-related tumor cell activities including angiogenesis, migration, invasion, and stemness. Owing to more effective drug administration, the metastasis suppression efficiency of GANT61 was significantly enhanced by the dual-targeting tLyP-1-rHDL delivery system. Meanwhile, the codelivery of paclitaxel and GANT61 by dual-targeting tLyP-1-rHDL nanoparticles demonstrated superior efficiency of disrupting proliferation and inducing apoptosis in tumor cells compared with drug solutions. In a spontaneous metastasis breast cancer NCG mice model, the tLyP-1-rHDL-PTX/GANT61 nanoparticles exhibited highly tumor-specific distribution and result in significant inhibition of the primary tumor growth and dramatic reduction of lung metastasis without obvious side effects. The present work suggests that a combination of the SHH signaling pathway suppression and chemotherapy assisted by peptide-functionalized targeting tLyP-1-rHDL nanoparticles may provide a promising strategy for metastatic TNBC treatment.

Background Ruptured abdominal aortic aneurysms have been a topic of common global interest for the past 20 years, with a steadily increasing number of publications. The purpose of this study was to explore the research themes and the current status of the last 10 years through a bibliometric analysis of the publications in this field. Material/Methods We performed a literature search for ruptured abdominal aortic aneurysms using the Web of Science Core Collection on November 14, 2021 and performed a bibliometric analysis and visualization of the results of the publications using the R-Bibliometrix package and VOSviewer software. Results From 2011 to 2020, 2381 publications were retrieved, including 2073 articles and 308 reviews. The United States had the highest number of publications and has made a large contribution to the field. Jonathan Golledge is an important researcher with the highest number of publications. Journal of Vascular Surgery is ranked first in terms of the number of publications and local citations. Mortality and outcomes, repair treatment, and risk factors are the 3 main focuses in the field, followed by intraluminal thrombus and molecular expression. Conclusions Our bibliometric analysis suggests mainstream research is focused on clinical studies related to the surgical approach and its prognosis and on pathological mechanisms and hemodynamic studies related to risk factors for abdominal aortic aneurysms rupture. There are many other opportunities for future research in the clinical joint basis of abdominal aortic aneurysms rupture.

Purpose To discuss the risk factors for abdominal aortic aneurysm rupture based on geometric and hemodynamic parameters. Methods We retrospectively reviewed the clinical data of those who were diagnosed with an abdominal aortic aneurysm by computed tomography angiography at our hospital between October 2019 and December 2020. Thirty-five patients were included in the ruptured group (13 patients) and the unruptured group (22 patients). We analyzed the differences and correlations of anatomical factors and hemodynamic parameters between the two groups using computational fluid dynamics based on computed tomography angiography. Results There were significant differences in the maximum diameter [(79.847 ± 10.067) mm vs. (52.320 ± 14.682) mm, P < 0.001], curvature [(0.139 ± 0.050) vs. 0.080 (0.123 − 0.068), P = 0.021], and wall shear stress at the site of maximal blood flow impact [0.549(0.839 − 0.492) Pa vs. (1.378 ± 0.255) Pa, P < 0.001] between the ruptured and unruptured groups, respectively. And in the ruptured group, wall shear stress at the rupture site was significantly different from that at the site of maximal blood flow impact [0.025 (0.049 − 0.018) Pa vs. 0.549 (0.839 − 0.492) Pa, P = 0.001]. Then, the maximum diameter and curvature were associated with rupture (maximum diameter: OR: 1.095, P = 0.003; curvature: OR: 1.142E + 10, P = 0.012). Most importantly, curvature is negatively correlated with wall shear stress (r = − 0.366, P = 0.033). Conclusions Both curvature and wall shear stress can evaluate the rupture risk of aneurysm. Also, curvature can be used as the geometric substitution of wall shear stress.

Purpose: Abdominal aortic aneurysm (AAA) is a severe cardiovascular disease that often results in high mortality due to sudden rupture. This paper aims to explore potential molecular mechanisms and effective targeted therapies to prevent and delay AAA rupture.Methods: We downloaded two microarray datasets (GSE98278 and GSE17901) from the Gene Expression Omnibus (GEO) database. Differential analysis and single-sample gene set enrichment analysis (ssGSEA) of hypoxia scores were performed on 48 AAA patients in GSE98278. We identified hypoxia- and ruptured AAA-related gene modules using weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the R package clusterProfiler. For candidate genes, validation was conducted on the mouse dataset GSE17901. Finally, we predicted drug candidates associated with the hub genes using the HERB Chinese medicine database.Results: Eighty-two differentially expressed genes were screened in the ruptured and stable groups; 103 differentially expressed genes were identified between the high- and low-hypoxia groups; and WGCNA identified 58 differentially expressed genes. Finally, nine candidate genes were screened, including two hub genes (MEDAG and SERPINE1). We identified pathways such as cytokine–cytokine receptor interaction and T-helper 1-type immune response involved in AAA hypoxia and rupture. We predicted 93 traditional Chinese medicines (TCMs) associated with MEDAG and SERPINE1.Conclusion: We identified the hypoxic molecules MEDAG and SERPINE1 associated with AAA rupture. Our study provides an additional direction for the association between hypoxia and AAA rupture.

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