Chemokines: Key Molecules that Orchestrate Communication among Neurons, Microglia and Astrocytes to Preserve Brain Function
NEUROSCIENCE
Authors: Trettel, Flavia; Di Castro, Maria Amalia; Limatola, Cristina
Abstract
In the CNS, chemokines and chemokine receptors are involved in pleiotropic physiological and pathological activities. Several evidences demonstrated that chemokine signaling in the CNS plays key homeostatic roles and, being expressed on neurons, glia and endothelial cells, chemokines mediate the bidirectional cross-talk among parenchymal cells. An efficient communication between neurons and glia is crucial to establish and maintain a healthy brain environment which ensures normal functionality. Glial cells behave as active sensors of environmental changes induced by neuronal activity or detrimental insults, supporting and exerting neuroprotective activities. In this review we summarize the evidence that chemokines (CXCL12, CX3CL1, CXCL16 and CCL2) modulate neuroprotective processes upon different noxious stimuli and participate to orchestrate neurons-microglia-astrocytes action to preserve and limit brain damage. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries. (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer
JOURNAL OF MATERIALS CHEMISTRY B
Authors: Ding, Lairong; Li, Junwei; Wu, Changrong; Yan, Feng; Li, Xuemei; Zhang, Shusheng
Abstract
The major drawbacks of traditional RNA cancer therapies include Low cellular uptake in vitro or in vivo, instability of in vivo circulation, nonspecific bio-distribution, and Lack of targeting ability, which result in poor silencing efficiency. Herein, we developed a novel RNA-triple-helix hydrogel for the treatment of triple negative breast cancers (TNBCs) by incorporating RNA-triple-helix and siRNA duplexes of CXCR4 into the same RNA nanoparticles with no synthetic polycationic reagents added. The RNA-triple-helix consists of one tumour suppressor miRNA (miRNA-205) and one oncomiR inhibitor (miRNA-221), both of which showed an outstanding effect in synergistically abrogating tumours. The siRNA duplexes of CXCR4 were embedded into the RNA hydrogel to block breast cancer metastasis and conjugation of the LXL-DNA aptamer (apt-DNA-Chol) is an effective target DNA sequence for MDA-MB-231 cells. The self-assembly of the RNA-triple-helix hydrogel exhibited high selectivity of in vitro and in vivo absorption and controlling miRNA expression when compared to free miRNA and RNA transcripts. The well-developed gene delivery system provided a potential treatment with high specificity and selectivity toward TNBCs. This strategy can be implemented in triplex-helix hydrogel design to form novel miRNA combinations to treat various human cancers.