Phenylalanine ammonia-lyase (PAL) is the first key enzyme of the phenypropanoid pathway. A full-length cDNA of PAL gene was isolated from Juglans regia for the first time, and designated as JrPAL. The full-length cDNA of the JrPAL gene contained a 1935bp open reading frame encoding a 645-amino-acid protein with a calculated molecular weight of about 70.4 kD and isoelectric point (pI) of 6.7. The deduced JrPAL protein showed high identities with other plant PALs. Molecular modeling of JrPAL showed that the 3D model of JrPAL was similar to that of PAL protein from Petroselinum crispum (PcPAL), implying that JrPAL may have similar functions with PcPAL. Phylogenetic tree analysis revealed that JrPAL shared the same evolutionary ancestor of other PALs and had a closer relationship with other angiosperm species. Transcription analysis revealed that JrPAL was expressed in all tested tissues including roots, stems, and leaves, with the highest transcription level being found in roots. Expression profiling analyses by real-time PCR revealed that JrPAL expression was induced by a variety of abiotic and biotic stresses, including UV-B, wounding, cold, abscisic acid and salicylic acid.
An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer‐derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer‐derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer‐derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis. Injury of peritoneal mesothelial cells elicited by gastric cancer‐derived exosomes is through concurrent apoptosis and mesothelial‐to‐mesenchymal transition (MMT). Additionally, upregulation of p‐ERK in peritoneal mesothelial cells is primarily responsible for the MMT while contributing little to apoptosis. Together, these data support the concept that exosomes play a crucial role in remodeling the premetastatic microenvironment and identify a novel mechanism for peritoneal metastasis of gastric carcinoma.
Magnetic nanoparticles have gained much interest for theranostics benefited from their intrinsic integration of imaging and therapeutic abilities. Herein, c(RGDyK) peptide PEGylated Fe@Fe O nanoparticles (RGD-PEG-MNPs) are developed for photoacoustic (PA)-enabled self-guidance in tumor-targeting magnetic hyperthermia therapy in vivo. In the α β -positive U87MG glioblastoma xenograft model, the PA signal of RGD-PEG-MNPs reaches its maximum in the tumor at 6 h after intravenous administration. This signal is enhanced by 2.2-folds compared to that of the preinjection and is also 2.2 times higher than that in the blocking group. It demonstrates the excellent targeting property of RGD-PEG-MNPs. With the guidance of the PA, an effective magnetic hyperthermia to tumor is achieved using RGD-PEG-MNPs.
Reactive
oxygen species (ROS)-based tumor therapy is still challenging
due to limited ROS-generating efficacy. Herein, we constructed heparin-conjugated
Fe@Fe3O4 NPs (Fe@Fe3O4@heparin, denoted as MNPs) as a peroxidase-mimicking nanozyme to
generate ROS for tumor therapy through the combination of the ultrasound-stimulated
Fenton reaction and the increased concentration of H2O2 by β-lapachone (La) in a tumor. La was first intraperitoneally
injected into mice and induced to generate a considerable quantity
of H2O2 through a specific tumor reaction, which
was catalyzed by MNPs to produce highly hydroxyl radicals (•OH).
Furthermore, the therapy efficacy for malignant tumors could significantly
be enhanced by an ultrasonic stimulation. With the help of the increased
amount of H2O2 generated by La in the tumor
and the enhanced peroxidase-mimicking activity of MNPs by ultrasound,
MNPs manifest good therapeutic performance in a 4T1 xenograft model,
which provides a strategy for enhanced nanozyme-mediated tumor therapy.
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