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Tea and citrus maxima are natural, medicinal homologous plants, typically used for making beverages, which have anticancer, antiobesity, and antioxidation properties. Green tea, yellow tea, and black tea were combined with citrus maxima to obtain green tea and Citrus maxima (GTCM), yellow tea and Citrus maxima (YTCM), and black tea and Citrus maxima (BTCM). The biochemical components of these mixtures were analyzed, and their possible effects and mechanisms on relieving liver lipid deposition were explored. The tea polyphenols, free amino acids, phenolamine ratio, and caffeine were comparable in YTCM and GTCM, being significantly higher than those in BTCM. In addition, the content of esterified catechins, nonesterified catechins, and total catechins in YTCM was significantly higher than those in GTCM and BTCM. All three mixtures of Citrus maxima tea significantly reduced lipid deposition in HepG2 cells, with GTCM and YTCM being slightly more effective than BTCM. Regarding the possible mechanism, Western blot analysis revealed that the three Citrus maxima tea mixtures could activate the AMPK/ACC signaling pathway, upregulate the expression of p-AMPK, p-ACC, and CPT-1 proteins, and downregulate the expression of SREBP1c and fatty acid synthase proteins to inhibit fat synthesis, thereby relieving lipid deposition in liver cells. In conclusion, as a novel and healthy beverage, Citrus maxima tea has the potential to alleviate liver lipid deposition, and further could be responsible for obesity treatment.

Antifungalmycin N2 (3-methyl-3,5-amino-4-vinyl-2-pyrone, C6H7O2N), was a novel and broad-spectrum antifungal metabolite produced by Streptomyces sp. N2. In the present work, antifungalmycin N2 was evaluated its induction of resistance against Rhizoctonia solani in rice seedling by measuring the defense-related physiological and biochemical parameters, such as the production of reactive oxygen species (ROS), the enzymatic activities involved in antioxidant systems (superoxide dismutase, SOD; catalase, CAT; peroxidase, POD), phenolics metabolism (phenylalanine ammonia-lyase, PAL; polyphenol oxidase, PPO), and pathogenesis-related proteins (β-1,3-glucanase and chitinase). It was found that the percentage disease index (PDI) of the R. solani-inoculated rice reduced from 65.21% to 26.02% when treated with 5.77 μg/ml antifungalmycin N2. Further results showed that the rice seedling could trigger its defense responses to R. solani infection by sharply accelerating the accumulation of ROS such as ·O2¬ and H2O2. But when the R. solani-inoculated rice was treated with antifungalmycin N2, the antioxidant SOD, CAT, and POD were significantly induced during the whole period of post inoculation (24–96 h), and consequently resulted in a sharp decline of ·O2¬ and H2O2 in rice seedlings. Compared with the R. solani-inoculated rice, the enzymatic activities of PPO, PAL, β-1,3-glucanase, and chitinase were significantly enhanced in the rice treated with antifungalmycin N2 plus R. solani. In conclusion, the above results suggested that antifungalmycin N2 could induce the resistance against R. solani in rice seedling by stimulating a series of defense responses, which would provide a comprehensive insight into the biocontrol function beyond its direct antagonistic activity against plant fungal pathogens.

Antifungalmycin N2 (3-methyl-3,5-amino-4-vinyl-2-pyrone, C6H7O2N) was a novel structural antifungal metabolite produced by Streptomyces sp. strain N2. Our previous study reported that the antagonistic interaction between antifungalmycin N2 and Rhizoctonia solani was accompanied by an oxidative stress in R. solani cell, indicating a probable damage occurred in the cell membranes and mitochondria. To verify this, the present study focused on investigating the effects of antifungalmycin N2 on the structure and function of cell membranes and mitochondria of R. solani. Morphological observations in transmission electron microscopy and fluorescence microscope showed that cell membranes of R. solani were damaged, and its cytoplasmic organelles were disorganized when treated with antifungalmycin N2. Meanwhile, the kinetics of membrane-related physiological and biochemical parameters, such as the increased malondialdehyde level, dropped ergosterol formation, and enhanced electrical conductivity in R. solani mycelia, further confirmed that antifungalmycin N2 would disrupt the cell membrane structure and function. More significantly, antifungalmycin N2 had a significantly inhibitory effect on the succinate dehydrogenase (SDH) activity of R. solani, and indicated that the mode and site of action of antifungalmycin N2 against R. solani might be similar to the existing succinate dehydrogenase inhibitors fungicides by binding in the ubiquinone-binding site. In conclusion, the above results demonstrated that the mode and site of action of antifungalmycin N2 targeted to cell membrane and SDH of R. solani, thus exerting the antifungal activity by damaging cell membrane structure and function, together with inhibiting the SDH activity.

Glioma is the most common type of malignant brain tumor. Phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has previously been identified as an oncoprotein that inhibits phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity. However, the role of PREX2a in the regulation of the malignant phenotype of glioma has yet to be reported. The present study demonstrated that the mRNA and protein expression levels of PREX2a were significantly increased in glioma tissue, as compared with in normal brain tissue. Furthermore, the expression levels of PREX2a were positively correlated with tumor grade. PREX2a‑specific small interfering RNA‑mediated knockdown significantly inhibited proliferation and induced apoptosis of SWO‑38 glioma cells. Furthermore, inhibition of PREX2a expression significantly suppressed cell cycle progression in glioma cells, as detected by cell cycle arrest at G1 phase. In addition, knockdown of PREX2a inhibited the invasion of SWO‑38 glioma cells. The present study also investigated the molecular mechanisms underlying the effects of PREX2a knockdown, and demonstrated that phosphoinositide 3‑kinase signaling was significantly downregulated, which may be due to the upregulation of PTEN activity. In conclusion, the present study is the first, to the best of our knowledge, to suggest that knockdown of PREX2a may effectively inhibit the malignant phenotype of glioma in vitro; therefore, PREX2a may be considered a potential molecular target for the treatment of glioma.

Background Sitagliptin is an anti-diabetic drug and its effects on Alzheimer’s disease (AD) remain controversial. This study aimed to investigate the protective effect of sitagliptin on the cognition in AD and its underlying molecular mechanism. Methods The APP/PS1 (a model of AD) mice received daily gastric gavage administration of sitagliptin (20 mg/kg) for 8 weeks. Then animals were subjected to behavioral experiment or sacrificed to histological staining and protein level analysis. Results The MWM test showed that sitagliptin treatment significantly reduced the escape latency times in APP/PS1 mice in the learning phase (day 3–5) and elongated the time spent in the target quadrant in the probe test. Sitagliptin significantly reduced amyloid plaque deposition and elevated the spine density and the protein levels of synaptoneurosome GluA1- and GluA2-containing AMPA receptor (GluA1R and GluA2R) in the brain of the APP/PS1 mice. Sitagliptin treatment significantly up-regulated the brain BNDF protein and phosphorylation of tyrosine receptor kinase B (TrkB). Furthermore, exendin-(9–39) (a glucagon-like peptide-1 [GLP-1] receptor antagonist) and K252a (a Trk tyrosine kinase inhibitor) treatment significantly abolished the cognitive protective effect of sitagliptin in the MWM test. Conclusion Sitagliptin treatment effectively protected the cognition function of the AD mice by regulating synaptic plasticity, at least partially, through activating GLP-1 and BDNF-TrkB signalings.

Study design A scanning electron microscopic study performed on three cadaveric specimens focused on the human suboccipital region, specifically, myodural bridge (MDB). Objective This study showed the connection form of the MDB among the suboccipital muscles, the posterior atlanto-occipital membrane (PAOM) and the spinal dura mater (SDM), and provided an ultrastructural morphological basis for the functional studies of the MDB. Summary of background data Since the myodural bridge was first discovered by Hack, researches on its morphology and functions had been progressing continuously. However, at present, research results about MDB were still limited to the gross anatomical and histological level. There was no research report showing the MDB's ultrastructural morphology and its ultrastructural connection forms between PAOM and SDM. Methods A scanning electron microscope (SEM) was used to observe the connection of myodural bridge fibers with PAOM and SDM in atlanto-occipital and atlanto-axial interspaces, and the connection forms were analyzed. Results Under the SEM, it was observed that there were clear direct connections between the suboccipital muscles and the PAOM and SDM in the atlanto-occipital and atlanto-axial spaces. These connections were myodural bridge. The fibers of the myodural bridge merged into the spinal dura mater and gradually became a superficial layer of the spinal dura mater. Conclusion MDB fibers merged into the SDM and became part of the SDM in the atlanto-occipital and atlanto-axial space. MDB could transfer tension and pulling force to the SDM effectively, during the contraction or relaxation of the suboccipital muscles. Level of evidence N/A.

Therapeutic targeting the protein-protein interaction (PPI) of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its main regulator, Kelch-like ECH-Associating protein 1 (Keap1) has been emerged as a feasible way to combat oxidative stress related diseases, due to the key role of Nrf2 in oxidative stress regulation. In recent years, many efforts have been made to develop potent Keap1-Nrf2 inhibitors with new chemical structures. Various molecules with diverse chemical structures have been reported and some compounds exhibit high potency. This review summarizes peptide and small molecule Keap1-Nrf2 inhibitors reported recently. We also highlight the pharmacological effects and discuss the possible therapeutic application of Keap1-Nrf2 inhibitors.

Purpose Functional MRI has played a fundamental role in Parkinson's disease(PD) study. In this paper, we performed an independent component analysis (ICA) based on functional networks to reveal the intricate variations on the morphology and functional properties of brain. Our analysis aims at discovering the differences between PD patients with sensorimotor function impairment and normal controls(NC), thus helping to understand the coordination neurological function degeneration in PD objectively. Method We investigated the blood oxygen level dependent(BOLD) functional MRI obtained at a 3.0 T MRI scanner. 30 PD patients and 28 NC subjects underwent the scan in resting state. The signals of sensory and motor coordinative control areas in the sensorimotor, insula and cerebellum networks acquired by ICA(Independent Component Analysis)were applied to analyze the functional alterations. Specifically, intra-network analysis was performed with signals in local networks, and inter-network analysis was conducted by functional network connectivity (FNC) with signals across different networks. Two sample T test was carried out to detect the significant (p Conclusion We identified an obvious increase in bilateral posterior insula, but decrease in bilateral cerebellum hemisphere, supplementary motor area(SMA) and precentral gyrus paracentral lobule of left postcentral gyrus. Besides, we found a significantly increased connection between independent component (IC) 13 which was located in right postcentral gyrus and cerebellum. Decreased connections were detected between sensory and motor cortex in sensorimotor network and between cerebellum and insula network by FNC analysis in PD patients as well. Discussion Parkinson's disease derives from the degeneration of the dopaminergic neurons in substantia nigra, and results in decreased secretion of inhibitory neurotransmitter. The significant differences between PD and NC groups in our research maybe explain the clinical manifestations of prominent bradykinesia and multiple extrapyramidal symptoms.

Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is st...

Liver cancer, one of the most common malignancies, is the second leading cause of cancer death in the world. The citrus reticulate peel and black tea have been studied for their beneficial health effects. In spite of the many studies have been reported, the underlying molecular mechanisms underlying its health benefits are still not fully understood. In present study, we developed a unique citrus reticulate peel black tea (CRPBT) by combined citrus reticulate peel and black tea and assessed its active ingredients, anti-oxidant and anti-liver cancer effects in vitro. The results suggested that CRPBT exhibited antioxidant capacity and effectively inhibited proliferation and migration of liver cancer cells in a dose- and time- dependent manner. Mechanistically, CRPBT significantly down-regulated phosphorylation of PI3K and AKT, and up-regulated the ratio of Bax/Bcl-2, and suppressed the expression of MMP2/9, N-cadherin and Vimetin proteins in liver cancer cells. Taken together, CRPBT has good effect on inhibiting migration, invasion, proliferation, and inducing apoptosis in liver cancer cells.

Warburg found that tumor cells exhibit high-level glycolysis, even under aerobic condition, which is known as the ‘Warburg effect’. As systemic changes in the entire metabolic network are gradually revealed, it is recognized that metabolic reprogramming has gone far beyond the imagination of Warburg. Metabolic reprogramming involves an active change in cancer cells to adapt to their biological characteristics. Thyroid cancer is a common endocrine malignant tumor whose metabolic characteristics have been studied in recent years. Some drugs targeting tumor metabolism are under clinical trial. This article reviews the metabolic changes and mechanisms in thyroid cancer, aiming to find metabolic-related molecules that could be potential markers to predict prognosis and metabolic pathways, or could serve as therapeutic targets. Our review indicates that knowledge in metabolic alteration has potential contributions in the diagnosis, treatment and prognostic evaluation of thyroid cancer, but further studies are needed for verification as well.

Background: Cytokine-induced killer (CIK) cells and natural killer (NK) cells are employed by two different approaches to adoptive cell immunotherapy for cancer. It has been reported that adoptive cell immunotherapy could prolong the overall survival (OS) of advanced cancer patients. The introduction of agents that induce immune checkpoint blockades has improved the efficacy of immune-mediated therapy for metastatic cancers. However, the effects of combining a checkpoint inhibitor with CIK cells or NK cells to target non-small cell lung cancer (NSCLC)remain unknown. Methods: The present study investigated the effects of combining CIK cells with a programmed cell death protein-1 (PD-1) inhibitor (an anti-PD-1 monoclonal antibody). During the expansion cultivation, the addition of the PD-1 antibody promoted CIK-mediated cytotoxicity in H1975 lung adenocarcinoma cells. Co-cultivation of CIK cells with the PD-1 antibody for 6 days induced CD3+CD56+ T cell expansion, with increases in the levels of CD107a and interferon γ (IFN-γ). Results: When NK cells were co-cultured with 5 μg/mL of an anti-programmed death-ligand 1 (PD-L1) mAb for 24 hours at an effector cell: target ratio of 10:1, it led to more potent cytotoxicity compared to other time points and concentrations. However, combining NK cells with the anti-PD-L1 mAb showed no significant advantages over treatment with NK cells alone. Conclusions: Our results suggest that combining CIK cells with PD-1 blockade before transfusion might improve the efficiency of CIK therapy for NSCLC patients. This effect does not seem to occur for NK cell therapy.

BACKGROUND/AIMS: Lung cancer is the leading cause of cancer-associated mortality worldwide. Long noncoding RNAs (lncRNAs) have been found to be related to different cancers and play important roles in regulating the pathological and physiological processes of numerous cancers. The aim of the current study was to identify potential prognostic long non-coding RNA biomarkers for predicting survival in patients with lung adenocarcinoma (LUAD) using The Cancer Genome Atlas (TCGA) dataset. METHODS: The clinical pathology and gene expression profiles of lung cancer were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs were identified and patient survival analysis performed. The prognostic signature was further evaluated by functional assessment and bioinformatics analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to predict the function of lncRNAs and to construct a gene co-expression network relationship to predict downstream target genes with the aid of the STRING database and Cytoscape software RESULTS: lncRNA RP11-434D9.1 and FENDRR had lower expression levels in lung cancer and were associated with poor prognoses. We found that the major functions of lncRNA RP1-434D9.1 and FENDRR were related to the cell cycle, and we further screened out the possible downstream target genes CDK1, CCNB1, CCNB2, CCNA1, AURKA, PLK1. CONCLUSIONS: LncRNA RP11-434D9.1 and FENDRR can be used as molecular biomarkers for the diagnosis and prognosis of lung adenocarcinoma. These dysregulated lncRNAs might negatively regulate cell cycle through the hub genes, which then affected cancer cell proliferation. These results may provide new ideas for further clinical research for markers used for lung cancer diagnosis and prognosis. FUNDING STATEMENT: This work was supported by National Natural Science Foundation of China (81672270); Key project of Guangzhou Science Technology and Innovation Committee (201707020042); Science and Technology Program of Guangzhou (201803010024); Science and Technology Planning Project of Guangdong Province, China (2017B020226005); Science and Technology Program of Guangzhou (201903010003). Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2016PY013); Scientific Research Projects of Wu Jieping Medical Research Foundation (320.6750.17206). DECLARATION OF INTERESTS: The authors declare that no conflicts of interest exist. ETHICS APPROVAL STATEMENT: Every specimen was anonymously handled based on ethical standards. All participants provided signed informed consent and our study had full approval from the hospital’s Ethical Review Committee.

Several studies have shown potent antineoplastic effects of tea, which can induce apoptosis and inhibit proliferation of cancer cells. Yellow tea is one of the six major types of tea, and yellowing time, a key factor in its processing, is known to improve its quality and bioactivity. However, the effects of yellowing on the composition of the bioactive substances of tea are poorly understood. We analyzed the biochemical composition and the antioxidant and anticancer activities of the extracts of yellow tea (EYTs) subjected to different yellowing durations. Prolonged yellowing increased the content of water extracts, amino acids, soluble sugars, theaflavins, and nonesterified catechins (p < 0.05, p < 0.01) and decreased that of polyphenols, flavonols, thearubigins, caffeine, GA, and esterified catechins (p < 0.05, p < 0.01). In addition, yellowing also slightly increased the antioxidant capacity of the EYTs, but did not significantly affect their ability to inhibit the proliferation of the hepatocarcinoma HepG2 cells. Mechanistically, the EYTs significantly downregulated the phosphorylation of PI3K and AKT and upregulated the Bax/Bcl‐2 ratio in the HepG2 cells. Taken together, the yellowing time influences the bioactive components of yellow tea, and the resulting yellow tea may have more potent antioxidant and anticancer effects.

Benefits of subdividing small-differentiated thyroid carcinoma (sDTC) by tumor size are controversial. We conducted a meta-analysis to investigate whether tumor size is associated with prognosis of sDTC. PubMed and Web of Science databases were searched from their inception to September 2018. The identified studies according to the inclusion/exclusion criteria were analyzed using fixed/random-effects models. Data were calculated and results of the meta-analysis were expressed as odd ratio (OR). sDTC was classified as S1 (≤1 cm) and S2 (>1 cm and ≤2 cm). A systematic analysis was performed to compare the difference of recurrence, survival and clinicopathological factors between the two subgroups of sDTC (S1 vs. S2). A total of 21 studies published between 2004 and 2017 enrolling 219,291 patients were included. Findings showed that, S2 was associated with higher recurrence risk compared with S1 (OR=1.575, 95% CI=1.428–1.738; P

Background: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. Methods: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed. We performed meta-analysis for data included in the selected literature, and then independently explored the correlation between genes by co-expression analysis of RNA-seq data in the TCGA database. Results: A sum of 9,934 lung cancer cases were collected from 34 published studies. Higher PD-L1 expression was associated with wild-type epidermal growth factor receptor (EGFR) [odds ratio (OR): 0.68, 95% confidence interval (CI): 0.48–0.96, P=0.03], Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (OR: 1.27, 95% CI: 1.02–1.58, P=0.03) or non-adenocarcinoma histology (OR: 0.68, 95% CI: 0.47–0.98, P=0.04). In addition, our analysis from TCGA data indicated that, compared with lung adenocarcinoma, the expression of PD-L1 was significantly higher than that of squamous cell carcinoma patients (P=0.023). The expression of targetable driver genes showed no correlations with PD-L1 expression in non-small cell lung cancer (NSCLC). Conclusions: Our results suggest the presence of EGFR wild-type, KRAS gene mutations or squamous cell carcinoma were associated with high PD-L1expression, which provides potential benefited population for the administration of PD-1/PD-L1 blockade in human lung cancer.

The metabolism of glucose is a nearly exclusive source of energy for maintaining neuronal survival, synaptic transmission and information processing in the brain. Two glucose metabolism pathways have been reported, direct neuronal glucose uptake and the astrocyte-neuron lactate shuttle (ANLS), which can be involved in these functions simultaneously or separately. Although ANLS in the dorsal hippocampus (DH) has been proved to be required for memory consolidation, the specific metabolic pathway involved during memory acquisition remains unclear. The DH and amygdala are two key brain regions for acquisition of contextual fear conditioning (CFC). In 2-NBDG experiments, we observed that 2-NBDG-positive neurons were significantly increased during the acquisition of CFC in the DH. However, in the amygdala and cerebellum, 2-NBDG-positive neurons were not changed during CFC training. Strikingly, microinjection of a glucose transporter (GLUT) inhibitor into the DH decreased freezing values during CFC training and 1 h later, while injection of a monocarboxylate transporter (MCT) inhibitor into the amygdala also reduced freezing values. Therefore, we demonstrated that direct neuronal glucose uptake was the primary means of energy supply in the DH, while ANLS might supply energy in the amygdala during acquisition. Furthermore, knockdown of GLUT3 by a lentivirus in the DH impaired the acquisition of CFC. Taken together, the results indicated that there were two different glucose metabolism pathways in the DH and amygdala during acquisition of contextual fear memory and that direct neuronal glucose uptake in the DH may be regulated by GLUT3.

Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2+/− and Uhrf2−/− mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.

Glioma is the most common type of malignant brain tumor. Phosphatidylinositol‑3,4,5‑trisphosphate‑dependent Rac exchange factor 2a (PREX2a), which is a regulator of the small guanosine triphosphatase Rac, has previously been identified as an oncoprotein that inhibits phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity. However, the role of PREX2a in the regulation of the malignant phenotype of glioma has yet to be reported. The present study demonstrated that the mRNA and protein expression levels of PREX2a were significantly increased in glioma tissue, as compared with in normal brain tissue. Furthermore, the expression levels of PREX2a were positively correlated with tumor grade. PREX2a‑specific small interfering RNA‑mediated knockdown significantly inhibited proliferation and induced apoptosis of SWO‑38 glioma cells. Furthermore, inhibition of PREX2a expression significantly suppressed cell cycle progression in glioma cells, as detected by cell cycle arrest at G1 phase. In addition, knockdown of PREX2a inhibited the invasion of SWO‑38 glioma cells. The present study also investigated the molecular mechanisms underlying the effects of PREX2a knockdown, and demonstrated that phosphoinositide 3‑kinase signaling was significantly downregulated, which may be due to the upregulation of PTEN activity. In conclusion, the present study is the first, to the best of our knowledge, to suggest that knockdown of PREX2a may effectively inhibit the malignant phenotype of glioma in vitro; therefore, PREX2a may be considered a potential molecular target for the treatment of glioma.

5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-kappaB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-alpha and IL-1beta in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction.