LncRNA nuclear-enriched abundant transcript 1 aggravates cerebral ischemia/reperfusion injury through activating early growth response-1/RNA binding motif protein 25 axis.

Ischemic stroke is a major global health issue. Ischemia and subsequent reperfusion results in stroke-related brain injury. Previous studies have demonstrated that nuclear-enriched abundant transcript 1 (NEATa and early growth response 1 (EGR1) are involved in ischemia reperfusion (IR) injury). In this study, we aimed to explore the roles of NEAT1/EGR1 axis as well as its downstream effector RNA binding motif protein 25 (RBM25) in cerebral IR injury. Oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO) were used to establish in vitro and in vivo models of cerebral IR injury, respectively. According to our data, NEAT1, EGR1, and RBM25 levels were elevated in OGD/R-exposed SK-N-SH and SH-SY5Y cells and cerebral cortex of MCAO mice. NEAT1, EGR1, or RBM25 knockdown effectively reduced infarct volumes and apoptosis, and improved neurological function. Mechanistically, NEAT1 directly interacted with EGR1, which restrained WW domain containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of EGR1 and subsequently caused EGR1 accumulation. EGR1 bound to RBM25 promoter and transcriptionally activated RBM25. Rescue experiments indicated that RBM25 overexpression abolished the therapeutic effects of NEAT1 knockdown. In conclusion, this work identified a novel NEAT1/EGR1/RBM25 axis in potentiating brain injury after IR insults, suggesting a potential therapeutic target for ischemic stroke.

IL-6-174 G/C and -572 C/G polymorphisms and risk of Alzheimer's disease.

Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer's disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR = 0.65, 95%CI = 0.52-0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR= 0.73, 95% CI = 0.62-0.86) and in additive model (GG vs. CC, OR= 0.66, 95% CI = 0.46-0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD.

Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients.

Osteopontin (OPN) and interleukin-23 (IL-23) are pro-inflammatory cytokines proposed to play central roles to the development of multiple sclerosis (MS). The aim of this study was to evaluate levels of OPN, IL-23 and other inflammatory cytokines and investigate their relationships in serum and cerebrospinal fluid (CSF) in patients with MS. Fifty one MS patients and 48 patients with non-inflammatory neurological diseases (NIND) were recruited from clinic. The levels of OPN, IL-23, IL-17, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in serum and CSF were determined in each participant. Compared with NIND group, MS patients had significantly elevated levels of OPN, IL-23, IL-17 and TNF-alpha in CSF, and elevated levels of IL-23, IL-17 and TNF-alpha in serum (All P<0.001). In MS patients, OPN and IL-23 were positively correlated with IL-17 (r=0.302, P=0.019; r=0.417, P=0.001, respectively); and IL-23 was positively correlated with EDSS (r=0.329, P=0.019). Both OPN and IL-23 may play pivotal role in development of MS and might be specific markers and therapeutic targets for MS.

Protective effect of edaravone against PrP106-126-induced PC12 cell death.

The prion protein peptide PrP106-126 induces cell apoptosis through mechanisms involving production of intracellular reactive oxygen species. The present study investigated the effects of edaravone, a potent free radical scavenger in clinical use, on cell cytotoxicity induced by PrP106-126. Results showed that PrP106-126 decreased PC12 cell viability in a dose- and time-dependent manner. Edaravone significantly antagonized the cytotoxic effects of PrP106-126. Mechanistically, PrP106-126 decreased PC 12 intracellular glutathione (GSH) concentrations, decreased superoxide dismutase (SOD) enzyme activity, increased concentrations of the oxidation end product malondialdehyde (MDA), depolarized the mitochondrial membrane, and increased caspase-3 activity. Edaravone alone did not affect GSH, SOD, or MDA but did effectively reverse all of the intracellular prooxidant effects induced by PrP106-126 and inhibit induced apoptosis in PC12 cells. In conclusion, edaravone may be a viable candidate for the treatment of oxidative stress-induced neurodegenerative disease.

[Expressions of heme oxygenase-1 and apoptosis-modulating proteins in peri-hematoma cortex after intracerebral hemorrhage in human being].

OBJECTIVE: To observe the expression of heme oxygenase-1 (HO-1) and Bcl-2, an apoptosis-modulating protein, in the neurons surrounding the hematoma in human being. METHODS: Specimens of cerebral cortex tissue 1 - 3 cm around the hemorrhagic focus with the size of 2.0 cm x 1.5 cm x 0.3 cm were collected during autopsy from 39 patients, 17 males and 22 females, aged 62.8 (36 - 84), who died from intracerebral hemorrhage 2 - 10 h, 17 - 30 h, 36 - 96 h, 120 - 216 h, or 240 - 408 h before. Specimens of brain tissue of the same size at the opposite side were collected as controls. Immunohistochemistry was used to examine the expression of HO-1 and Bcl-2 protein. RESULTS: (1) Expression of HO-1 could be detected in the specimens of the 2 h group, increased in the specimens of the 2 - 10 h group [(5.1 +/- 2.0)/HP], reached the peak in the 17 - 30 h group [(11.3 +/- 0.9)/HP], then began to decrease in the specimens of the 240 - 408 h group [(6.4 +/- 0.6)/HP] (F = 42.80, P < 0.001). The HO-1 expression of the control group remained negative at any time-point. (2) Expression of Bcl-2 could be detected in the specimens of the 2 - 10 h group [(4.2 +/- 1.7)/HP], was increased in the 17 - 30 h group [(6.6 +/- 0.5)/HP], reached the peak in the 36 approximately 96 h group [(8.9 +/- 1.1)/HP], then began to decrease, and was (4.7 +/- 0.6)/HP in the 240 approximately 408 h group (F = 29.59, P < 0.001). The Bcl-2 expression remained negative at any time point in the control group. (3) The expressions of HO-1 was positively correlated with the expression of Bcl-2 (r = 0.66, P < 0.001). CONCLUSIONS: Over-expression of HO-1 and Bcl-2 in the neurons provide a potential protection or destruction mechanism after intracerebral hemorrhage in human.