We showed that the engineered GnRH-hpRNase1 can specifically target the GnRH receptor-expressing cells and inhibit their proliferation through inducing apoptosis. Owing to its promising anti-tumor activity, the fusion enzyme can be further examined on GnRH-R-expressing tumor xenografts to evaluate its anti-tumor effects in vivo.
In summary, the mutation of rln3a in male tilapia resulted in notable changes in circadian rhythm and disease-linked signaling pathways in the Di* and Hyp. These changes might account for the fertility defects observed in rln3a-/- male mutants in tilapia.
The MOA of female reproductive toxicity caused by BPS at human-relevant levels might involve: molecular initiating event (MIE)-BPS binding to ERβ receptor, key event (KE)1-the interrupted expression of GnRH, KE2-the activation of JNK (for short-term exposure) and ERK pathway (for long-term exposure), KE3-cell cycle arrest (the increased percentage of the G0/G1 phase), and KE4-interruption of cell proliferation (only for short-term exposure). The BMDL of the percentage of the S phase after 24 h exposure was the lowest among all the BMDLs of a good fit, with BMDL of 9.55 μM.
11 months ago
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EGFR (Epidermal growth factor receptor) • ER (Estrogen receptor) • MAPK1 (Mitogen-activated protein kinase 1) • MAPK8 (Mitogen-activated protein kinase 8)
Another recent approach based on this knowledge was the use of GnRH peptides for developing specific targeted therapies, improving the delivery and accumulation of drugs in tumoral cells, and decreasing most side effects of current treatments. In this review, we discuss the conventional uses of GnRH analogs, together with the recent advances in GnRH-based drug delivery for ovarian, breast, and prostatic cancer cells.
Furthermore, the caspase 3/7 assay demonstrated apoptosis in the MCL-1 silenced tissues. The study strongly suggests that targeted delivery of siRNAs using multi-layered dendrimer nanostructures could be an effective therapy for LHRH overexpressing cancers.
It was also found that UTMD-mediated delivery of shRNA-Livin notably declined the mRNA and protein expression levels of caspase-3 and caspase-8 in OVCA-433 cells compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. Our experiment verifies the hypothesis that ultrasound mediation of targeted microbubbles can enhance the transfection efficiency of shRNA-Livin in ovarian cancer cells.
Besides the selective targeting that the specific conjugate could offer, we also recorded high internalization levels in T24 bladder cancer cells. The ruthenium(ii) polypyridyl peptide-based conjugates we developed is an intriguing approach that offers targeted cell imaging in the Near Infrared region, and simultaneously paves the way for further advancements in the dynamic studies on cellular imaging.