Peritoneal dialysis reduces amyloid-beta plasma levels in humans and attenuates Alzheimer-associated phenotypes in an APP/PS1 mouse model.

Clearance of amyloid-beta (Aß) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aß clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aß, suggesting that the peripheral approach of removing Aß from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aß burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aß concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from 6 months of age (prevention study) or 9 months of age (treatment study). The Aß in the interstitial fluid (ISF) was collected using microdialysis. Behavioural performance, long-term potentiation (LTP), Aß burden and other AD-type pathologies were measured after 1 month of peritoneal dialysis. Peritoneal dialysis significantly reduced plasma Aß levels in both CKD patients and APP/PS1 mice. Aß levels in the brain ISF of APP/PS1 mice immediately decreased after reduction of Aß in the blood during peritoneal dialysis. In both prevention and treatment studies, peritoneal dialysis substantially reduced Aß deposition, attenuated other AD-type pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, and synaptic dysfunction, and rescued the behavioural deficits of APPswe/PS1 mice. Importantly, the Aß phagocytosis function of microglia was enhanced in APP/PS1 mice after peritoneal dialysis. Our study suggests that peritoneal dialysis is a promising therapeutic method for AD, and Aß clearance using a peripheral approach could be a desirable therapeutic strategy for AD.

MicroRNA-1304 suppresses human non-small cell lung cancer cell growth in vitro by targeting heme oxygenase-1.

Previous studies have shown that microRNA-1304 (miR-1304) is dysregulated in certain types of cancers, including non-small cell lung cancer (NSCLC), and might be involved in tumor survival and/or growth. In this study we investigated the direct target of miR-1304 and its function in NSCLC in vitro. Human lung adenocarcinoma cell lines (A549 and NCI-H1975) were studied. The cell proliferation and survival were investigated via cell counting, MTT and colony-formation assays. Cell apoptosis and cell cycle were examined using annexin V-PE/7-AAD and PI staining assays, respectively. The dual-luciferase reporter assay was used to verify post-transcriptional regulation of heme oxygenase-1 (HO-1) by miR-1304. CRISPR/Cas9 was used to deplete endogenous miR-1304. Overexpression of MiR-1304 significantly decreased the number and viability of NSCLC cells and colony formation, and induced cell apoptosis and G0/G1 phase cell cycle arrest. HO-1 was demonstrated to be a direct target of miR-1304 in NSCLC cells. Restoration of HO-1 expression by hemin (20 µmol/L) abolished the inhibition of miR-1304 on cell growth and rescued miR-1304-induced apoptosis in A549 cells. Suppression of endogenous miR-1304 with anti-1304 significantly increased HO-1 expression and promoted cell growth and survival in A549 cells. In 17 human NSCLC tissue samples, miR-1304 expression was significantly decreased, while HO-1 expression was significantly increased as compared to normal lung tissues. MicroRNA-1304 is a tumor suppressor and HO-1 is its direct target in NSCLC. The results suggest the potential for miR-1304 as a therapeutic target for NSCLC.

[Moderate Angiogenic Effect of Xuefu Zhuyu Capsule by Regulating EphB4/EphrinB2].

Objective To observe moderate angiogenic effect of Xuefu Zhuyu Capsule (XFZYC) on human microvascular endothelial cell line 1 ( HMEC-1) , and its regulation effect on expression of EphB4/EphrinB2. Methods The moderate angiogenic effect of XFZYC was clarified by detecting XFZYC containing serum on cell viability, cell cycle, migration, adhesion and in vitro angiogenesis. Its effects on expressions of EphB4/EphrinB2 were detected by Real-time quantitative PCR and Western blot. Results XFZYC containing serum (XFZYC-CS) had no effect on the cell viability or cell ratio in phase S endothelial cells. Cell migration was significantly improved by 1.25% XFZYC-CS after 24, 48, and 72 h of action 2. 50% XFZYC-CS inhibited cell migration at the primary 24 h, but it significantly promoted cell migration at 48 and 72 h afterwards. It showed just an opposite tendency to 5. 00% XFZYC-CS. Cellular adhesion number was significantly reduced by 1. 25% XFZYC-CS at 72 h. Cellular adhesion number was significant- ly increased by 2. 50% XFZYC-CS at 24 and 48 h, but inhibited at 72 h 5. 00% XFZYC-CS showed inhibition at 24 h, but turned to promotion, and disappeared afterwards. In vessel formation aspect, only 2.50% XFZYC-CS showed vessel formation promotion 5. 00% XFZYC-CS showed inhibition on vessel formation at 48 and 72 h. Results of Real-time quantitative PCR and Western blot in 2. 50% XFZYC-CS showed EphB4 expression was up-regulated at 12 h; EphB4 expression was down-regulated while EphrinB2 expression was up-regulated at 24 h. Conclusions Only 2. 50% XFZYC-CS at 48 h had promotion of migration, adhe- sion, and in vitro angiogenesis of HMEC-1 , which was the optimal condition for vessel growth. These re- sults suggested XFZYC promoted angiogenesis in certain conditional limitations. But it regulated the ex- pression of EphB4/EphrinB2, which might be one of important factors.

[Roles of bFGF in endothelial cell tube formation induced by xuefu zhuyu decoction under non-anoxia condition].

OBJECTIVE: To explore the roles of basic fibroblast growth factor (bFGF) on tube formation induced by xuefu zhuyu decoction (XZD) under non-anoxia condition. METHODS: Using serum pharmacology technique, endothelial cell line ECV304 cells were incubated in routine 95% O2. ECV304 cells were intervened by 1.25%, 2.50%, and 5.00% XZD containing serums and the vehicle serum for 48 h. The effects of XZD on tube formation, bFGF contents and its transcription levels were assessed by in vitro tube formation assay, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. RESULTS: Three concentrations of XZD containing serums could not only obviously promote the tube formation bFGF level, but also up-regulate bFGF contents in the supernate and its transcription levels. The shapes of lumens were more regular in those induced by 1.25% and 2.50% XZD containing serums. CONCLUSION: XZD induced angiogenesis via up-regulating the bFGF expression under non-anoxia condition.

[Essential role of TRPC6 in the proliferation of gastric cancer and its mechanism].

OBJECTIVE: To investigate the essential role and mechanism of TRPC6 gene in the development of gastric cancer. METHODS: The expression of TRPC6 protein was assessed in gastric cancer tissues and normal tissues adjacent to the cancer from 30 patients with gastric cancer. The inhibiting effect of TRPC6 activity on cell growth, cell cycle of a human gastric cancer cell line AGS cells, tumor progression and development of xenografted human gastric cancer in a mouse model was tested using dominant-negative mutant TRPC6 (DNC6). The survival of mice bearing xenografted tumors in the GFP and DNC6 was compared using Kaplan-Meier analysis. All statistical tests were two-sided. RESULTS: The TRPC6 protein in the tumor tissues and para-tumor tissues was (21.60 ± 8.32)% versus (7.14 ± 2.24)%. After transfection of DNC6 virus for 24 hours, 48 hours, 72 hours and 96 hours, the growth inhibition rates of gastric cancer cells were (36.90 ± 1.13)%, (44.06 ± 2.17)%, (52.12 ± 2.76)% and (50.89 ± 1.97)%, respectively. The clone formation rates of control group and DNC6 group were (14.70 ± 3.00)% versus (43.80 ± 7.00)%. After transfection with DNC6 virus for 0, 24, 36 and 48 hours, the G(2)/M phase arrest was (20.34 ± 1.98)%, (24.31 ± 2.37)%, (27.70 ± 2.36)%, (35.10 ± 3.0)% in the DNC6 group and (18.40 ± 2.01)%, (18.0% ± 1.72)%, (17.50 ± 1.74)%, (16.80 ± 1.71)% in the control group, respectively. Inhibition of TRPC6 activity also reduced the subcutaneous tumor volume in the mouse models with xenografted human tumors (P < 0.05). CONCLUSION: In the preclinical models tested, TRPC6 channels are essential for gastric cancer development via regulation of G(2)/M phase transition.

Diffusion tensor imaging of the hippocampus reflects the severity of hippocampal injury induced by global cerebral ischemia/reperfusion injury.

At present, predicting the severity of brain injury caused by global cerebral ischemia/reperfusion injury (GCI/RI) is a clinical problem. After such an injury, clinical indicators that can directly reflect neurological dysfunction are lacking. The change in hippocampal microstructure is the key to memory formation and consolidation. Diffusion tensor imaging is a highly sensitive tool for visualizing injury to hippocampal microstructure. Although hippocampal microstructure, brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) levels are closely related to nerve injury and the repair process after GCI/RI, whether these indicators can reflect the severity of such hippocampal injury remains unknown. To address this issue, we established rat models of GCI/RI using the four-vessel occlusion method. Diffusion tensor imaging parameters, BDNF, and TrkB levels were correlated with modified neurological severity scores. The results revealed that after GCI/RI, while neurological function was not related to BDNF and TrkB levels, it was related to hippocampal fractional anisotropy. These findings suggest that hippocampal fractional anisotropy can reflect the severity of hippocampal injury after global GCI/RI. The study was approved by the Institutional Animal Care and Use Committee of Capital Medical University, China (approval No. AEEI-2015-139) on November 9, 2015.

Minimal alveolar concentration of sevoflurane in combination with dexmedetomidine in patients with hysteroscopy: An up-down sequential allocation study.

BACKGROUND: Dexmedetomidine is commonly used in hysteroscopy surgery due to its analgesia and sedation without respiratory depression. Many studies have shown that dexmedetomidine can reduce the consumption of sevoflurane. However, the optimal end-tidal concentration of sevoflurane when it is co-administered with dexmedetomidine has not been established. The primary purpose of this study was to investigate the minimal alveolar concentration (MAC) of sevoflurane for cervical dilatation combined with different doses of dexmedetomidine in patients with hysteroscopy surgery. METHODS: One-hundred patients undergoing hysteroscopy surgery were enrolled in this clinical trial. All the patients were randomly assigned into four groups (C, D1 , D2 , D3 ) and received a loading dose of dexmedetomidine (0, 0.6, 0.8 and 1.0 µg/kg) over 10 min before anaesthesia induction, respectively. Anaesthesia was induced in each patient with 5% sevoflurane in 100% oxygen via a facemask. A laryngeal mask (LMA) was inserted when the patient had lost consciousness and the BIS value decreased below 40. The response to cervical dilatation stimulus (movement vs non-movement) by the insert of hysteroscope was recorded. The MAC of sevoflurane was measured by up and down sequential method of Dixon and Mood and centred isotonic regression analysis. RESULTS: The calculated MAC of sevoflurane using up-and-down method of Dixon and Mood in patients with hysteroscopy surgery was (1.90 ± 0.13)%, (1.23 ± 0.16)%, (1.03 ± 0.10)% and (0.93 ± 0.08)% in groups C, D1 , D2 and D3 , respectively. CONCLUSIONS: The administration of dexmedetomidine can significantly decrease the MAC of sevoflurane for hysteroscopy surgery. However, a ceiling effect of the reduction was observed when the dose of dexmedetomidine was higher than 0.8 µg/kg.

Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is known to promote neuronal survival and differentiation and to guide axon extension both in vitro and in vivo. The BDNF-induced chemo-attraction of axonal growth cones requires Ca2+ signalling, but how Ca2+ is regulated by BDNF at the growth cone remains largely unclear. Extracellular application of BDNF triggers membrane currents resembling those through TRPC (transient receptor potential canonical) channels in rat pontine neurons and in Xenopus spinal neurons. Here, we report that in cultured cerebellar granule cells, TRPC channels contribute to the BDNF-induced elevation of Ca2+ at the growth cone and are required for BDNF-induced chemo-attractive turning. Several members of the TRPC family are highly expressed in these neurons, and both Ca2+ elevation and growth-cone turning induced by BDNF are abolished by pharmacological inhibition of TRPC channels, overexpression of a dominant-negative form of TRPC3 or TRPC6, or downregulation of TRPC3 expression via short interfering RNA. Thus, TRPC channel activity is essential for nerve-growth-cone guidance by BDNF.

OIP5-AS1 specifies p53-driven POX transcription regulated by TRPC6 in glioma.

Transcription factors (TFs) control an array of expressed genes. However, the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown. Here, in TRPC6-regulated proline oxidase 1 (POX) transcription in human glioma, we report that OIP5-AS1, a long noncoding RNA, determines the specificity of p53-driven POX expression. The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription. An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription. Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development. Thus, the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.

[Screening and identification of differential expression genes related to stress fracture by cDNA microarray assay].

OBJECTIVE: To evaluate the differentially expressed genes between the Stress fracture (SF) cases and controls. METHODS: Total RNA was extracted and purified from peripheral blood sample of 3 SF cases and 3 controls who conducted a 1:1 matched case-control study, then used for Human Genome Array analysis. The hybridization data were analyzed using SAM software. Parts of these genes were analyzed and identified by real-time PCR. RESULTS: Upregulated and downregulated genes were 22 and 1, respectively. Thus the highest ratio and most significant cytokine was tumor necrosis factor receptor superfamily, member 10c (TNFRSF10C). The result of real-time PCR shows that TNFRSF10C was over-expressed in 3 cases and low-expressed in 1 case. CONCLUSION: Obvious difference exists in gene expression between SF cases and controls, showing there may be a lot of genes involving in the occurrence and development of SF. Meanwhile, the identification of the specific genes is helpful for biomechanics study, early diagnosis and screening of SF.

A novel low-cost electrode for recording the local field potential of freely moving rat's brain.

Local field potentials (LFPs) are involved in almost all cognitive activities of animals. Several kinds of recording electrodes are used for recording LFPs in freely moving animals, including commercial and homemade electrodes. However, commercial recording electrodes are expensive, and their relatively fixed size often causes a steric hindrance effect, especially when combining deep brain stimulation (DBS) with LFP recording, which may not always satisfy the aim of researchers. Currently, an increasing number of researchers are designing their own recording electrodes to lower research costs. Nevertheless, there is no simple universal method to produce low-cost recording electrodes with a specific size according to the target brain area. Thus, we developed a simple method for quickly producing low-cost multiple-channel recording electrodes. To inspect the effectiveness of our self-designed electrode, LFPs were recorded in a Parkinson's disease (PD) rat model, and an electrical stimulation electrode was implanted into the subthalamic nucleus to verify the space-saving ability of the self-designed recording electrode. The results showed that <30 min was needed to prepare an electrode and that the electrode materials cost <5 dollars. Further investigations showed that our electrode successfully recorded the beta oscillations (12-40 Hz) in the PD rat model. Thus, this method will greatly reduce the cost of recording electrodes and save time for researchers. Additionally, the small size of the electrode will further facilitate DBS research.

The synthesis of ursolic acid derivatives with cytotoxic activity and the investigation of their preliminary mechanism of action.

Nineteen ursolic acid derivatives (15 novel compounds) modified at the C-3 and the C-28 positions were synthesized. The cytotoxic activity of the derivatives was evaluated against HeLa, BGC-823 and SKOV3 cells by MTT assay. Inducing apoptosis and affecting cell cycle distribution by the derivatives in HeLa cells were assessed by flow cytometry and DNA fragmentation. Compounds 10b and 11b were particularly active to inhibit HeLa cells growth through inducing apoptosis and arresting cell cycle progression. The typical 'sub-G1 peak' and DNA ladder formation were checked and cell cycle was arrested at the S phase in a dose-dependent manner.

Effect of proliferation, cell cycle, and Bcl-2s of MCF-7 cells by resveratrol.

Our goals were to examine the dual-directional regulation effects of resveratrol (1) in vitro by using MCF-7 cells (estradiol receptor-positive cells), study its mechanism of action, and give a systematical analysis of the regulatory networks of each related factor. An MTT test and growth curve showed that the proliferation of MCF-7 cells was inhibited by a high concentration of 1, and that its IC(50) was 8.70 x 10(-5) +/- 0.23 mol/l. However, 1 induced the proliferation of MCF-7 cells at 10(-7)-10(-5) mol/l, and resulted in a peak proliferation at 1.0 x 10(-7) mol/l. A high concentration of 1 arrested cell cycle progression at the G(1) phase, and a typical "sub-G(1) peak" of apoptotic cells was also observed by flow cytometry. The proliferation index of MCF-7 cells increased significantly with a low concentration of 1 (p < 0.05). 1 in high concentrations induced Bax, caspase-3, and cyclin-dependent kinase (CDK) inhibitor P21 expression, whereas the expressions of cyclin CDK2, Bcl-2, and proliferating cell nuclear antigen (PCNA) were decreased by 1 treatment. Conversely, treatment with low concentrations of 1 decreased the expression of P21 and Bax, while the expressions of cyclin CDK2, Bcl-2, and PCNA were increased. These results suggest that 1 had a dual-regulatory effect on MCF-7 cells. CDK-associated protein was a key factor at both the high and low concentrations used in this study.

Effects of osthole on apoptosis and TGF-beta1 of hypertrophic scar fibroblasts.

Osthole, 7-methoxy-8-[3-methylpent-2-enyl]coumarin (1), was extracted from a Chinese herb Cnidium monnieri (L.) Cuss. It showed immunity strengthening, anti-tumor, anti-hepatitis, and anti-osteoporosis activities in previous studies. Our goals are to study the effects of 1 on cell proliferation and TGF-beta of hypertrophic scar fibroblasts. Our results showed that 1 induced apoptosis and inhibited cell proliferation in hypertrophic scar fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that its IC(50) value toward hypertrophic scar fibroblasts was 15.5 +/- 2.2 micromol/l. Furthermore, the results of cell growth curve matched with the above results. Inducing apoptosis by 1 in hypertrophic scar fibroblasts was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. A typical 'Sub-G(1) peak' was also checked through flow cytometry. We used immunohistochemistry to observe the expression of TGF-beta(1). Also, we found that 1 could obviously inhibit the expression of TGF-beta(1) of fibroblasts derived from hypertrophic scar compared with the control group (P < 0.05). These results suggest that 1 inhibits the growth of hypertrophic scar fibroblasts through apoptosis and decreases the expression of TGF-beta(1).

Intracranial Medulloepithelioma in a Child: A Case Report.

Intracranial medulloepithelioma is an extremely rare and highly malignant fast-growing tumor that shows a propensity to spread widely throughout the central nervous system. It most commonly occurs in infants and young children. We report a rare case of 2-year-old female patient with a large mass lesion diagnosed as medulloepithelioma. Although radiological examination was characteristic for the neoplasm, it was not sufficient to make a definite diagnosis. However, when it was combined with histopathological examination, we could diagnose medulloepithelioma and differentiate it from other central nervous system tumors. We intend to provide greater understanding and knowledge of intracranial medulloepithelioma by reporting this case.

A novel mutation in a common pathogenic gene (SETD5) associated with intellectual disability: A case report.

Intellectual disability (ID) is a non-specific phenotype present in a genetically heterogeneous group of disorders. The genetic cause of ID remains elusive in the majority of patients due to this extreme heterogeneity. Whole exome sequencing technology has been applied to identify pathogenic gene variants responsible for ID. The present report described a 1.7-year-old female patient who had severe ID with the specific features of delayed motor development, language disorders and abnormal facial features. Exome analysis identified a novel pathogenic variant of the SETD5 gene [c.2025_2026delAG (p.Gly676Valfs*2)]. The variant was a frameshift mutation, causing termination of the protein in advance. These findings indicated that this mutation of the SETD5 gene may be a genetic cause for ID. The present study aimed to provide a meaningful exploration of ID and the identification of clinical core genetic pedigrees.

Author Correction: Candida albicans gains azole resistance by altering sphingolipid composition.

In the original version of this Article, Haoping Liu, who conceptualized, designed and supervised the project and acquired funding, was inadvertently omitted from the author list. Furthermore, the affiliation of Jiaxin Gao and Haoping Liu with 'Department of Biological Chemistry, University of California, Irvine, CA 92697, USA' was omitted. Finally, funding from NIH grant GM117111, and contributions from Dr. Li-lin Du of NIBS for providing pPB[ura4] and pDUAL-PBase and Allan Bradley of Sanger for hyPBase, were not acknowledged. These errors have now been corrected in both the PDF and HTML versions of the Article.

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway.

BACKGROUND: Neural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring. METHODS: We conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones. RESULTS: There were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271-13.258; OR = 3.333, 95%CI: 1.068-10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070-3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023-3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361-11.308). CONCLUSION: Folic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.

Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation.

beta-Elemene, a natural plant drug extracted from Curcuma wenyujin, has been used as an antitumor drug for different tumors, including glioblastoma. However, the mechanism of its anti-tumor effect is largely unknown. Here we report that anti-proliferation of glioblastoma cells induced by beta-elemene was dependent on p38 MAPK activation. Treatment of glioblastoma cell lines with beta-elemene, led to phosphorylation of p38 MAPK, cell-cycle arrest in G0/G1 phase and inhibition of proliferation of these cells. Inhibition of p38 MAPK reversed beta-elemene-mediated anti-proliferation effect. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of beta-elemene. Taken together, our findings indicate that activation of p38 MAPK is critical for the anti-proliferation effect of beta-elemene and that p38 MAPK might be a putative pharmacological target for glioblastoma therapy.

[Effect of p38 MAPK on elemene-induced cell cycle arrest in C6 glioblastoma cells].

OBJECTIVE: To observe the effect of elemene on cell cycle of rat C6 glioblastoma cells. METHODS: Cell cycle analysis and expression of p38 in C6 glioblastoma cells under elemene treatment were measured by flow cytometry and Western blot. Flow cytometry and MTT assay were used to examine cell cycle and cell proliferation while C6 glioblastoma cells were pretreated with p38 inhibitor and DN-p38 plasmids. RESULTS: The fraction of C6 in the G0/G1 phase increased 11%, 6.95%, 19.57% respectively in the presence of 40, 60 and 80 microg/ml elemene. The level of phosphorylated p38 MAPK was greatly increased in a dose and time-dependent manner. Inhibition of p38 MAPK activation with SB203580 and DN-p38 blocked elemene-induced anti-proliferation effect. CONCLUSION: Elemene could induce G0/G1 cell cycle phase arrest of C6 glioblastoma cells through up-regulation of phosphorylated p38.