Background: Evidence has demonstrated that non-coding RNAs (ncRNAs) could be delivered efficiently to recipient cells using exosomes as a carrier. Additionally, long ncRNA nuclear enriched abundant transcript 1 (NEAT1) is emerging as a vital regulatory molecule in the progression of rheumatoid arthritis (RA). The aim of this study was to identify the NEAT1/miR-144-3p/Rho-associated protein kinase 2 (ROCK2) functional network regulating the WNT signaling pathway in RA. Methods: In vivo, a collagen-induced arthritis (CIA) model was established to analyze the effects of blood exosomes on the incidence, clinical score, and bone degradation of RA. In vitro, the CD4+T cells were characterized by flow cytometry and the cell activities were analyzed in the presence of exosome treatment alone or in combination with altered expression of NEAT1, miR-144-3p or Rho-associated protein kinase 2 (ROCK2). The expression of NEAT1, miR-144-3p, ROCK2, and corresponding proteins in the WNT signaling pathway was detected by RT-qPCR and western blot techniques. The binding profile of NEAT1 to miR-144-3p was evaluated via a combination approach of luciferase activity assay, RNA immunoprecipitation, and RNA pull-down experiments. Results: Blood exosomes extracted from RA patients increased the incidence of RA and bone destruction significantly. Overexpression of NEAT1 or ROCK2 promoted immune cell (CD4+T cells) proliferation, Th17 cell differentiation, and cell migration in response to stimulus, whereas knockout of the NEAT1 gene induced the expression of miR-144-3p in CD4+T cells. ROCK2 exogenous expression inhibited the expression of miR-144-3p, inducing activation of the WNT signaling pathway. Conclusion: A novel regulatory pathway NEAT1/miR-144-3p/ROCK2/WNT in RA was investigated as a potential target for RA therapy.

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Onyx is increasingly used in endovascular therapy of intracranial arteriovenous malformations (AVMs). However, the embolic effect and post-embolization management are still under discussion. We report our experience in the treatment of supratentorial brain arteriovenous malformations (SBAVMs) with Onyx and discuss post-embolic management. From June 2006 to July 2008, 20 patients with SBAVM were embolized with Onyx. There were 14 men and six women ranging from 14 to 64 years of age (mean 38.3 years). Initial symptoms included spontaneous hemorrhage (n=12), headaches (n=4), seizure (n=3) and incidentally disclosed after head trauma (n=1). After the endovascular procedure, all had subsequent treatment (follow-up angiogram, stereotactic radiosurgery or microsurgery) according to the obliteration degree. At angiography, seven patients (35%, 7/20) were completely obliterated (over 95% closure) after embolization while one suffered a small subarachnoid hemorrhage without permanent clinical sequelae. Four patients (20%, 4/20) were subtotally obliterated (over 80% closure), one patient who suffered severe cerebral edema after embolization underwent decompressive craniectomy, two patients had additional radiosurgery and one patient had follow-up angiogram. Nine patients (45%, 9/20) were partially obliterated (20–80% closure), five patients had additional surgery, two patients had additional radiosurgery and two patients had follow-up angiogram (one patient had intraventricular hemorrhage three months after embolization). Of all 20 AVMs, an average of 2.2 ml Onyx was used per patient and average volume reduction was 80% (range, 30%–99%). Onyx is suitable for embolization of SBAVMs because of its diffuse controllable properties. We suggest clinical follow-up after complete obliteration, additional radiosurgery or angiographic follow-up after subtotal obliteration and additional surgery after partially obliteration. More cases with long-term follow-up are needed to evaluate the long-term prognosis of our post-embolization management.

Although microRNA-144-3p (miRNA-144-3p) has been shown to suppress tumor proliferation and invasion, its function in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) remains unclear. Thus, this study was designed to investigate the role of miRNA-144-3p in ICH. To accomplish this, we used adult male Sprague-Dawley rats to establish an in vivo ICH model by injecting autologous blood, while cultured primary rat cortical neurons were exposed to oxyhemoglobin (OxyHb) to mimic ICH in vitro. To examine the role of miRNA-144-3p in ICH-induced SBI, we used an miRNA-144-3p mimic and inhibitor both in vivo and in vitro. Following ICH induction, we found miRNA-144-3p expression to increase. Additionally, we predicted the formyl peptide receptor 2 (FPR2) to be a potential miRNA-144-3p target, which we validated experimentally, with FPR2 expression downregulated when miRNA-144-3p was upregulated. Furthermore, elevated miRNA-144-3p levels aggravated brain edema and neurobehavioral disorders and induced neuronal apoptosis via the downregulation of FPR2 both in vivo and in vitro. We suspected that these beneficial effects provided by FPR2 were associated with the PI3K/AKT pathway. We validated this finding by overexpressing FPR2 while inhibiting PI3K/AKT in vitro and in vivo. In conclusion, miRNA-144-3p aggravated ICH-induced SBI by targeting and downregulating FPR2, thereby contributing to neurological dysfunction and neural apoptosis via PI3K/AKT pathway activation. These findings suggest that inhibiting miRNA-144-3p may offer an effective approach to attenuating brain damage incurred after ICH and a potential therapy to improve ICH-induced SBI.