ABSTRACT
Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAFs) play an important role in prostate tumor metastasis by shaping the malignant tumor microenvironment. Herein, we constructed a CAF-targeting siRNA delivery system by loading the fibroblast activation protein-α (FAP-α) antibody onto the cell-penetrating peptide (CPP)-based nanoparticles, which specifically downregulated C-X-C motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation generated a series of changes through inactivating CAFs so that the malignant prostate tumor microenvironment was reshaped. The tumor cell invasion, migration, and tumor angiogenesis were significantly inhibited, which all contributed to the suppression of the metastasis of an orthotopic prostate tumor. This tumor microenvironment reshaping strategy via CAF targeting and inactivation provides an alternative approach for malignant prostate tumor metastasis inhibition.
Subject(s)
Cancer-Associated Fibroblasts , Nanomedicine/methods , Prostatic Neoplasms , Tumor Microenvironment , Animals , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/metabolism , Cell-Penetrating Peptides/chemistry , Cell-Penetrating Peptides/pharmacology , Chemokine CXCL12/genetics , Chemokine CXCL12/metabolism , Endopeptidases , Gelatinases/antagonists & inhibitors , Gelatinases/metabolism , Gene Silencing , Human Umbilical Vein Endothelial Cells , Humans , Male , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/metabolism , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/chemistry , Neoplasm Metastasis/prevention & control , PC-3 Cells , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , RNA, Small Interfering , Serine Endopeptidases/metabolism , Tumor Microenvironment/drug effects , Tumor Microenvironment/physiologyABSTRACT
An observability condition number is defined for physical systems modeled by network dynamics. Assuming that the dynamical equations of the network are known and a noisy trajectory is observed at a subset of the nodes, we calculate the expected distance to the nearest correct trajectory as a function of the observation noise level and discuss how it varies over the unobserved nodes of the network. When the condition number is sufficiently large, reconstructing the trajectory from observations from the subset will be infeasible. This knowledge can be used to choose an optimal subset from which to observe a network.
ABSTRACT
Volatile essential oils (EOs), non-volatile rutin (RU), quercetin (QU), kaempferol (KA) and isorhamnetin (IS) were effectively extracted and isolated from seabuckthorn (Hippophae rhamnoides L.) leaves by ionic liquid-based ultrasound/microwave-assisted simultaneous distillation extraction (ILUMASDE). After optimization by response surface methodology, EOs, RU, QU, KA and IS were separated under the following optimum conditions: an ionic liquid of 1.0 M 1-butyl-3-methyl imidazole bromine salt ([C4mim]), liquid/solid ratio of 12 ml g-1, extraction time of 34 min, microwave power of 540 W and a fixed ultrasonic power of 50 W. Under the optimized conditions of ILUMASDE, the extraction yields of RU, QU, KA, IS and EOs were 9.18 ± 0.35, 5.52 ± 0.23, 3.03 ± 0.11, 5.64 ± 0.24 mg g-1 and 0.095 ± 0.004%, respectively. The yield of EOs obtained using ILUMASDE was 1.07-fold higher than that obtained by conventional hydrodistillation extraction (HDE). In addition, the components of the EOs obtained using ILUMASDE and HDE were similar. The extraction yields of RU, QU, KA, IS obtained by ILUMASDE were 1.03-1.35-fold higher than that obtained by the ethanol ultrasonic-assisted extraction (EUAE), ionic liquid-based ultrasonic-assisted extraction (ILUAE) and ionic liquid-based microwave-assisted extraction (ILMAE). And the extraction time used by ILUMASDE was 34 min, which is 14.17%, 56.67%, 56.67% and 85.00% less than those used by HDE, EUAE, ILUAE and ILMAE, respectively. Therefore, ILUMASDE can be considered a rapid and efficient method for extracting flavonoids and EO from seabuckthorn (Hippophae rhamnoids L.) leaves.
