[Corrigendum] Quercetin protects rat cortical neurons against traumatic brain injury.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of the data panels in Fig. 4A (on p. 7862), showing the 'Sham' and 'TBI' experiments, were overlapping, such that the data were apparently derived from the same original source. After having examined their original data, the authors have realized that they uploaded the incorrect image for the 'Sham' experiment in this figure. The revised version of Fig. 4 showing the correct data for all the experiments portrayed in Fig. 4A, is shown opposite. Note that the replacement of the erroneous data does not affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for granting them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused.[Molecular Medicine Reports 17: 7859-7865, 2018; DOI: 10.3892/mmr.2018.8801].

Upregulation of KIF11 in TP53 Mutant Glioma Promotes Tumor Stemness and Drug Resistance.

Glioma is the most common type of primary brain malignancy with high morbidity and mortality, but little is known about its pathological mechanisms. Kinesin family member 11 (KIF11) is a key driver of malignancy in glioblastoma, a grade IV glioma, but its involvement in glioma chemoresistance remains to be determined. We accessed the TCGA open datasets, collected glioma tumor tissue samples, and analyzed the expression of KIF11 in glioma patients. Meanwhile, the correlation between KIF11 and survival outcomes was determined by the Kaplan-Meier analysis. The role of KIF11 in glioma tumor cell function was assessed in an in vitro knockdown and overexpressing system. Here, we found that KIF11 was upregulated in glioma tumors and negatively correlated with overall survival outcomes via analyzing the open datasets. KIF11 was negatively correlated with TP53 expression. Furthermore, KIF11 promoted the stemness in glioma cells, accompanied by increased cell proliferation and chemoresistance. Mechanistically, we found that KIF11 promoted cell cycle progression via upregulating cyclin expression.

Protective effects of quercetin on traumatic brain injury induced inflammation and oxidative stress in cortex through activating Nrf2/HO-1 pathway.

BACKGROUND: Traumatic brain injury (TBI) has been a serious public health issue. Clinically, there is an urgent need for agents to ameliorate the neuroinflammation and oxidative stress induced by TBI. Our previous research has demonstrated that quercetin could protect the neurological function. However, the detailed mechanism underlying this process remains poorly understood. OBJECTIVE: This research was designed to investigate the mechanisms of quercetin to protect the cortical neurons. METHODS: A modified weight-drop device was used for the TBI model. 5, 20 or 50 mg/kg quercetin was injected intraperitoneally to rats at 0.5, 12 and 24 h post TBI. Rats were sacrificed three days post injury and their cerebral cortex was obtained from the injured side. The rats were randomly assigned into three groups of equal number: TBI and quercetin group, TBI group, and Sham group. The brain water content was calculated to estimate the brain damage induced by TBI. Immunohistochemical and Western blot assays were utilized to investigate the neurobehavioral status. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction were performed to evaluate the inflammatory responses. The cortical oxidative stress was measured by estimating the activities of malondialdehyde, superoxide dismutase, catalase and glutathione-Px. Western blot was utilized to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). RESULTS: Quercetin attenuated the brain edema and microgliosis in TBI rats. Quercetin treatment attenuated cortical inflammatory responses and oxidative stress induced by TBI insults. Quercetin treatment activated the cortical Nrf2/HO-1 pathway in TBI rats. CONCLUSIONS: Quercetin ameliorated the TBI-induced neuroinflammation and oxidative stress in the cortex through activating the Nrf2/HO-1 pathway.

Inhibition of RNF6 alleviates traumatic brain injury by suppressing STAT3 signaling in rats.

BACKGROUND: Traumatic brain injury (TBI) has ranked as one of the leading causes of disability and death in the world. The neuroinflammation mediated by signal transducer and activator of transcription 3 (STAT3) signaling during the progression of TBI leads to long-term neurodegeneration. Ring finger protein 6 (RNF-6) is an E3 ubiquitin ligase and can regulate the activity of STAT3 signaling pathway by targeting its inhibitors. However, the mechanism underlying this process in TBI remains poorly understood. METHODS: In this research, cortical impact injury was used to construct the TBI rat model. Western blot assay was performed to evaluate the protein levels of RNF6, Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), and STAT3/pSTAT3. QRT-PCR assay was performed to assess the RNA levels of RNF6 and other cytokines. The neural function of TBI rats was estimated by modified Neurological Severity Scores test. RESULTS: The expression of RNF-6 was up-regulated in the brain tissues of TBI rats. Down-regulation of RNF6 alleviated the symptoms and improved the neural recovery postinjury in TBI rats. Inhibition of RNF6 suppressed the cerebral inflammation by up-regulating the protein level of SHP-1 and down-regulating the phosphorylation level of STAT3. CONCLUSION: Inhibition of RNF6 alleviated TBI by suppressing the STAT3 signaling in TBI rats.

Quercetin protects rat cortical neurons against traumatic brain injury.

Previous studies have demonstrated that traumatic brain injury (TBI) may cause neurological deficits and neuronal cell apoptosis. Quercetin, one of the most widely distributed flavonoids, possesses anti­inflammatory, anti­blood coagulation, anti­ischemic and anti­cancer activities, and neuroprotective effects in the context of brain injury. The purpose of the present study was to investigate the neuroprotective effects of quercetin in TBI. A total of 75 rats were randomly arranged into 3 groups as follows: Sham group (Sham); TBI group (TBI); and TBI + quercetin group (Que). Brain edema was evaluated by analysis of brain water content. The neurobehavioral status of the rats was evaluated by Neurological Severity Scoring. Immunohistochemical and western blot analyses were used to measure the expression of certain proteins. The results of the present study demonstrated that post­TBI administration of quercetin may attenuate brain edema, in addition to improving motor function in rats. Additionally, quercetin caused a marked inhibition of extracellular signal­regulated kinase 1/2 phosphorylation and activated Akt serine/threonine protein kinase phosphorylation, which may result in attenuation of neuronal apoptosis. The present study provided novel insights into the mechanism through which quercetin may exert its neuroprotective activity in a rat model of TBI.

Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K/Akt signaling pathway.

OBJECTIVE: Neuronal autophagy and apoptosis play an irreplaceable role in brain injury pathogenesis and may represent a hopeful target for treatment. Previous studies have demonstrated that administration of quercetin-attenuated brain damage in a variety of brain injury models including traumatic brain injury (TBI). However, whether PI3K/Akt signaling pathway mediates the neuroprotection of quercetin following TBI is not well clarified. We sought to propose a hypothesis that quercetin could attenuate neuronal autophagy and apoptosis via enhancing PI3K/Akt signaling. METHODS: All rats were randomly arranged into four groups as follows: sham group (n = 25), TBI group (n = 25), TBI + quercetin group (n = 25), TBI + quercetin + LY294002 group (n = 25). Quercetin (Sigma, USA, dissolved in 0.9% saline solution) was administered intraperitoneally at a dose of 50 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and spatial cognitive function was assessed by the neurologic severity score and Morris water maze, respectively. Immunohistochemistry staining and western blotting was used to evaluate the expression of LC3, p-Akt, caspase-3, Bcl-2, and Bax. RESULTS: Quercetin treatment significantly attenuated TBI-induced neurological impairment (1-3 days, p < 0.05) and improved cognitive function (5-8 days, p < 0.05). Double immunolabeling demonstrated that quercetin significantly reduced the LC3-positive cells co-labeled with NeuN, whereas significantly enhanced p-Akt-positive cells co-labeled with NeuN. Furthermore, quercetin treatment reduced the expression of LC3、caspase-3 and Bax levels induced following TBI (p < 0.05), and increased the expression of p-Akt and Bcl-2 at 48 h (p < 0.05). CONCLUSION: In conclusion, our observations indicate that post-injury treatment with quercetin could inhibit neuronal autophagy and apoptosis in the hippocampus in a rat model of TBI. The neuroprotective effects of quercetin may be related to modulation of PI3K/Akt signaling pathway.