Naltrexone is neuroprotective against traumatic brain injury in mu opioid receptor knockout mice

AimsNaltrexone is a mu opioid receptor (MOR) antagonist used to treat drug dependence in patients. Previous reports indicated that MOR antagonists reduced neurodegeneration and inflammation after brain injury. The purpose of this study was to evaluate the neuroprotective effect of naltrexone in cell culture and a mouse model of traumatic brain injury (TBI).MethodsThe neuroprotective effect of naltrexone was examined in primary cortical neurons co‐cultured with BV2 microglia. Controlled cortical impact (CCI) was delivered to the left cerebral cortex of adult male MOR wild‐type (WT) and knockout (KO) mice. Naltrexone was given daily for 4 days, starting from day 2 after lesioning. Locomotor activity was evaluated on day 5 after the CCI. Brain tissues were collected for immunostaining, Western, and qPCR analysis.ResultsGlutamate reduced MAP2 immunoreactivity (‐ir), while increased IBA1‐ir in neuron/BV2 co‐culture; both responses were antagonized by naltrexone. TBI significantly reduced locomotor activity and increased the expression of IBA1, iNOS, and CD4 in the lesioned cortex. Naltrexone significantly and equally antagonized the motor deficits and expression of IBA1 and iNOS in WT and KO mice. TBI‐mediated CD4 protein production was attenuated by naltrexone in WT mice, but not in KO mice.ConclusionNaltrexone reduced TBI‐mediated neurodegeneration and inflammation in MOR WT and KO mice. The protective effect of naltrexone involves non‐MOR and MOR mechanisms.     

Nobiletin,a Polymethoxylated Flavone,Inhibits Glioma Cell Growth and Migration via Arresting Cell Cycle and Suppressing MAPK and Akt Pathways

Nobiletin, a bioactive polymethoxylated flavone (5,6,7,8,3^',4^'‐hexamethoxyflavone), is abundant in citrus fruit peel. Although nobiletin exhibits antitumor activity against various cancer cells, the effect of nobiletin on glioma cells remains unclear. The aim of this study was to determine the effects of nobiletin on the human U87 and Hs683 glioma cell lines. Treating glioma cells with nobiletin (20–100 µm ) reduced cell viability and arrested the cell cycle in the G0/G1 phase, as detected using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and propidium iodide (PI) staining, respectively; however, nobiletin did not induce cell apoptosis according to PI‐annexin V double staining. Data from western blotting showed that nobiletin significantly attenuated the expression of cyclin D1, cyclin‐dependent kinase 2, cyclin‐dependent kinase 4, and E2 promoter‐binding factor 1 (E2F1) and the phosphorylation of Akt/protein kinase B and mitogen‐activated protein kinases, including p38, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase. Our data also showed that nobiletin inhibited glioma cell migration, as detected by both functional wound healing and transwell migration assays. Altogether, the present results suggest that nobiletin inhibits mitogen‐activated protein kinase and Akt/protein kinase B pathways and downregulates positive regulators of the cell cycle, leading to subsequent suppression of glioma cell proliferation and migration. Our findings evidence that nobiletin may have potential for treating glioblastoma multiforme. Copyright © 2015 John Wiley & Sons, Ltd.     

Intrathoracic caudate lobe of the liver:A case report and literature review

Heterotopic supradiaphragmatic livers are rare.A total of 23 cases of primary supradiaphragmatic livers have been reported in the literature.The clinical presentations of heterotopic supradiaphragmatic liver are variable.The simultaneous detection of intrathoracic accessory liver and pulmonary sequestration is extremely rare,and only one case has previously been reported.It is difficult to make a correct diagnosis preoperatively.We presented a 53-year-old woman with complaints of an intermittent,productive cough and dyspnea for two months that was refractory to medical treatment.She had no previous history of trauma or surgery.A chest radiograph only showed a widening of the mediastinum.Contrast-enhanced computed tomography of the chest revealed a well-circumscribed homogenous soft-tissue mass,approximately 4.35 cm×2.5 cm×6.14 cm in size,protruding through the right diaphragmatic crura to the right pleural cavity,attached to the inferior vena cava,esophagus and liver.There was no conclusive diagnosis before surgery.After the operation,we discovered that this patient was the first case of a supradiaphragmatic heterotopic liver,which passed through the inferior vena cava foramen and was coincidentally combined with an intralobar pulmonary sequestration that was found intraoperatively.We discussed its successful management with surgical resection via a thoracic approach and reviewed the published literature.     

Increase of toll-like receptor 4 but decrease of interleukin-8 mRNA expression among ischemic stroke patients under aspirin treatment

ObjectivesToll-like receptors (TLRs) are molecules conserved in evolution for detecting pathogen invasions and tissue damage and are involved in atherogenesis. This study explores the mRNA expression of TLRs and their probable role in further disease occurrence among ischemic stroke patients.Design and MethodsA total of 89 ischemic stroke patients and 166 controls were recruited for this study. Total RNA was extracted and mRNA was reverse-transcribed to cDNA and was analyzed for TLRs and interleukin 8 (IL8).ResultsThe TLR4 mRNA expression level is significantly higher in the stroke group. Conversely, IL-8 mRNA levels decreased significantly in the patient group.ConclusionOur results suggest that TLR4 overexpression in mRNA levels is observed in stroke patients, which might account for the probable inflammatory injury before or after stroke. A reduction of IL-8 expression could result from the downregulatory effects of aspirin.     

Retraction: Effects of a transtheoretical model–based exercise stage–matched intervention on exercise behaviour and quality of life in patients with coronary heart disease: a randomized controlled trial

The above article from Journal of Advanced Nursing, published online on 26th June 2014 in Wiley Online Library ( wileyonlinelibrary.com ) has been retracted by agreement between the journal Editor‐in‐Chief and John Wiley & Sons Ltd. The retraction has been agreed due to considerable overlap with the following papers: Zhu L.‐X., Ho S.‐C., Sit J.W.H., He H.‐G. (2014) Effect of a transtheoretical model‐based stage‐matched exercise intervention on exercise behavior and angina in patients with coronary heart disease: a randomized controlled trial. Journal of Cardiovascular Nursing DOI: 10.1097/JCN.0000000000000162 . Zhu L.‐X., Ho S.‐C., Sit J.W.H., He H.‐G. (2014) The effects of a transtheoretical model‐based exercise stage‐matched intervention on exercise behavior in patients with coronary heart disease: A randomized controlled trial. Patient Education and Counseling 95, 384–392. Reference Zhu L‐X., Ho S‐C., Sit J.W.H. & He H‐G. (2014) Effects of a transtheoretical model–based exercise stage–matched intervention on exercise behaviour and quality of life in patients with coronary heart disease: a randomized controlled trial. Journal of Advanced Nursing. doi: 10.1111/jan.12469     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.