Electroacupuncture Pretreatment Prevents Cognitive Impairment Induced by Cerebral Ischemia–Reperfusion via Adenosine A1 Receptors in Rats

A previous study has demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. In the present study, we investigated whether adenosine receptor 1 (A1 R) is involved in EA pretreatment-induced cognitive impairment after focal cerebral ischemia in rats. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 min in male Sprague-Dawley rats. The neurobehavioral score, cognitive function [as determined by the Morris water maze (MWM) test], neuronal number, and the Bax/Bcl-2 ratio was evaluated at 24 h after reperfusion in the presence or absence of CCPA (a selective A1 receptor agonist), DPCPX (a selective A1 receptor antagonist) into left lateral ventricle, or A1 short interfering RNA into the hippocampus area. The expression of the A1 receptor in the hippocampus was also investigated. The result showed that EA pretreatment upregulated the neuronal expression of the A1 receptor in the rat hippocampus at 90 min. And EA pretreatment reversed cognitive impairment, improved neurological outcome, and inhibited apoptosis at 24 h after reperfusion. Pretreatment with CCPA could imitate the beneficial effects of EA pretreatment. But the EA pretreatment effects were abolished by DPCPX. Furthermore, A1 receptor protein was reduced by A1 short interfering RNA which attenuated EA pretreatment-induced cognitive impairment.

Redox Responsive Pluronic Micelle Mediated Delivery of Functional siRNA: A Modular Nano-Assembly for Targeted Delivery

There is an unmet need to develop strategies that allow site-specific delivery of short interfering RNA (siRNA) without any associated toxicity. To address this challenge, we have developed a novel...

Investigating histidinylated highly branched poly(lysine) for siRNA delivery

The temporary silencing of disease-associated genes utilising short interfering RNA (siRNA) is a potent and selective route for addressing a wide range of life limiting disorders. However, the few clinically...

ARPC4 gene silencing inhibits T24 cell invasion and metastasis via a mechanism involving Arp2/3/cofilin-1 signaling pathway

Purpose: To study the influence of ARPC4 gene silencing on human urinary bladder cancer (T24) cell proliferation, invasiveness and migration, and the mechanism(s) involved.Methods: Short interfering RNA (siRNA) ARPC4 silencing fragment was transfected into T24 cells. Transfection efficiency was measured with qRT-PCR. Cell proliferation, invasiveness and migratory potential were determined with CCK-8, Transwell invasion assay, and immunofluorescence assay,respectively. Protein expressions of ARPC4 and cofilin-1 were assayed using Western blotting.Results: Short interfering RNA (siRNA) silencing of ARPC4 gene led to the downregulation of mRNA and protein expressions of ARPC4 (t = 14.898, p < 0.05; t = 7.686, p < 0.05). It also significantly downregulated cofilin-1 protein, while inhibiting proliferative capacity, invasiveness and pseudopodiaformation capacity of T24 cells (t = 8.042, p < 0.05).Conclusion: The results obtained suggest that ARPC4 gene silencing inhibits T24 cell invasion and metastasis via a mechanism involving regulation of the Arp2/3/cofilin-1 signaling route. This provides new leads for gene therapy. Keywords: ARPC4, Bladder carcinoma, Gene silencing, Invasiveness, Cell proliferation