Angiostrongylus Cantonensis-Conditioned Culture Medium Induces Myelin Basic Protein Alterations via Erk1/2 and NF-κB Activation in Rat RSC96 Schwann Cells.

Eating of excessive raw or undercooked environmental snails produces angiostrongyliasis demyelination caused by Angiostrongylus cantonensis (A. cantonensis). The aim of this study was to investigate the association between extracellular signal-regulated kinase (Erk)1/2-nuclear factor (NF)-κB pathway and myelin basic protein (MBP) expression in RSC96 Schwann cells treated with A. cantonensis-conditioned culture medium, which was prepared by culturing the third-stage (L3) nematode larvae in DMEM for 72 h. The supernatants were collected and filtered before use. Our results showed that MBP was produced in the RSC96 cells at 16 h to 48 h post-stimulation (PS). Phosphorylated (p)-NF-κB levels were significantly increased from 8 h to 48 h PS, as were the p-Erk1/2 levels at the same time points. Additionally, expression of p-NF-κB and MBP was significantly decreased by treatment with QNZ, an NF-κB inhibitor. Treatment with PD98059, an Erk kinase inhibitor, efficiently reduced p-Erk1/2, p-NF-κB and MBP expression in the Schwann cells. These results suggest that A. cantonensis-conditioned culture medium induced suppression of the Erk1/2-NF-κB signaling pathway leading to reduced MBP production in RSC96 Schwann cells. Thus, inhibiting this signaling intermediate involved in MBP expression may be a potential method for controlling inflammatory development of A. cantonensis-induced MBP changes in preceded demyelination.

Glucose Transporter Type 4 Redistribution on the Membrane Induced by Insulin through Akt in Hydrocortisone Treatment in Rat Skeletal Muscles.

Hydrocortisone is a growth hormone frequently used in the treatment of low back pain. Hydrocortisone treatment has an anti-inflammation effect, which also inactivates glucose transporter type 4 (GLUT4) by p38 mitogen-activated protein kinase (MAPK) inhibition. Translocation of GLUT4 regulates body glucose homeostasis and muscle repair and is induced by insulin. In this study, 56 SD rats were divided into seven groups, and were treated with insulin or hydrocortisone in sedentary or exercise training groups. The muscle proteins and biochemical blood parameters were analyzed after 7 days of treatments. The results showed that the serum glucose increased in hydrocortisone treatment accompanied by GLUT4 inactivation in both the sedentary and exercise training rats. In the exercise training groups, GLUT4 was redistributed on the plasma membrane on co-treatment with insulin and hydrocortisone through Akt phosphorylation. Insulin treatment exerted a compensatory feedback effect on the GLUT4 translocation on hydrocortisone co-treatment, which was the cause of GLUT4 inactivation.

Tumor cycling hypoxia induces chemoresistance in glioblastoma multiforme by upregulating the expression and function of ABCB1.

Tumor cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. However, how tumor cycling hypoxia impacts chemotherapy is unclear. In the present study, we explored the impact and the mechanism of cycling hypoxia on tumor microenvironment-mediated chemoresistance. Hoechst 33342 staining and hypoxia-inducible factor-1 (HIF-1) activation labeling together with immunofluorescence imaging and fluorescence-activated cell sorting were used to isolate hypoxic tumor subpopulations from human glioblastoma xenografts. ABCB1 expression, P-glycoprotein function, and chemosensitivity in tumor cells derived from human glioblastoma xenografts or in vitro cycling hypoxic stress-treated glioblastoma cells were determined using Western blot analysis, drug accumulation and efflux assays, and MTT assay, respectively. ABCB1 expression and P-glycoprotein function were upregulated under cycling hypoxia in glioblastoma cells concomitant with decreased responses to doxorubicin and BCNU. However, ABCB1 knockdown inhibited these effects. Moreover, immunofluorescence imaging and flow cytometric analysis for ABCB1, HIF-1 activation, and Hoechst 3342 in glioblastoma revealed highly localized ABCB1 expression predominantly in potentially cycling hypoxic areas with HIF-1 activation and blood perfusion in the solid tumor microenvironment. The cycling hypoxic tumor cells derived from glioblastoma xenografts exhibited higher ABCB1 expression, P-glycoprotein function, and chemoresistance, compared with chronic hypoxic and normoxic cells. Tumor-bearing mice that received YC-1, an HIF-1α inhibitor, exhibited suppressed tumor microenvironment-induced ABCB1 induction and enhanced survival rate in BCNU chemotherapy. Cycling hypoxia plays a vital role in tumor microenvironment-mediated chemoresistance through the HIF-1-dependent induction of ABCB1. HIF-1 blockade before and concurrent with chemotherapy could suppress cycling hypoxia-induced chemoresistance.

Extracranial-intracranial (EC-IC) bypass of symptomatic middle cerebral artery (MCA) total occlusion for haemodynamic impairment patients.

A retrospective, single-centre, non-randomized study in the management of symptomatic middle cerebral artery (MCA) total occlusion disease to evaluate extracranial-intracranial (EC-IC) bypass as an intervention for patients with atherosclerotic MCA total occlusion, ischemic symptoms (transient ischemic attacks [TIAs]) or poor cerebral haemodynamics who had not responded well to maximal medical treatment was reported. Twenty-three patients were included in the study with the criteria of: having ischemic syndrome, for example, TIA; being associated with atherosclerotic MCA total occlusion disease (compatible with radiological assessment); being failed to respond to optimal medical therapy (e.g. antiplatelet therapy), indicating a repeat TIA or ischemic stroke attack was noted during maximal medical therapy; having poor cerebral perfusion on CT imaging; and having regional cerebrovascular reactivity (rCVR) of <20% when acetazolamide challenge was undergone. Patients had acute ischemic stroke or other major medical co-morbidities were excluded. No patient experienced any recurrent ischemic stroke during a mean follow-up period of 26.5 months except one patient suffered of immediate post-operative ischemic stroke because of the temporal vessel being clipped too long and the hypotension caused by anaesthesia. Post-operative follow-up imaging, which included MRI (MR angiography) and four-vessel digital subtraction angiography revealed a 100% patency of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. No significant differences between observation periods (baseline status: 5.46 ± 5.13/85 ± 15; 0.5 month after surgery: 5.18 ± 5.29/85.91 ± 15.46 and 3 months after surgery: 5.09 ± 4.75/85.36 ± 12.27) were found for the neurological evaluations of NIHSS and Barthel Index (both expressed in mean ± SD) in all of the 23 patients. The annual risk of recurrent stroke was 0% after EC-IC bypass. However, studies with a larger scale are warranted to further confirm the effectiveness of EC-IC bypass.

Butylidenephthalide suppresses human telomerase reverse transcriptase (TERT) in human glioblastomas.

BACKGROUND: Telomerase is widely expressed in most human cancers, but is almost undetectable in normal somatic cells and is therefore a potential drug target. Using the human telomerase promoter platform, the naturally occurring compound butylidenephthalide (BP) was selected for subsequent investigation of antitumor activity in vitro and in vivo. METHODS: We treated human glioblastoma cells with BP and found a dose-dependent decrease in human telomerase reverse transcriptase (hTERT) mRNA expression and a concomitant increase in p16 and p21 expression. Because c-Myc and Sp1 are involved in transcriptional regulation of hTERT, the effect of BP on c-Myc and Sp1 expression was examined. RESULTS: Using electrophoretic mobility shift assays and western blotting, we showed that BP represses hTERT transcriptional activity via downregulation of Sp1 expression. Using the telomerase repeat amplification protocol, an association between BP concentration and suppression of telomerase activity, induction of human glioblastoma senescence, and inhibition of cellular proliferation was identified. This was supported by a mouse xenograft model, in which BP repressed telomerase and inhibited tumor proliferation, resulting in tumor senescence. Overexpression of hTERT restored telomerase activity in human glioblastoma cells and overcame replicative senescence. CONCLUSIONS: These findings suggest that BP inhibits proliferation and induces senescence in human glioblastomas by downregulating hTERT expression and consequently telomerase activity. This is the first study to describe regulation of telomerase activity by BP in human glioblastomas.

Dislodged upper thoracic cage in the gastrointestinal tract: a case report and literature reviews.

STUDY DESIGN: A rare case of esophageal perforation secondary to a dislodged upper thoracic cage found by the gastrointestinal endoscope is presented. OBJECTIVE: To report an extremely rare complication of upper thoracic vertebral tuberculosis treated with corpectomy and interbody cage surgery and suggest the cause, mechanism, and outcome of the complication of esophageal perforation. SUMMARY OF BACKGROUND DATA: Tuberculotic spondylitis often affects the anterior column of the spine and surgery is indicated in the presence of an epidural abscess, neurologic deficits secondary to compression of the spinal cord, bone destruction with instability, or failure of antituberculous therapy. Surgical treatment requires radical debridement followed by anterior stabilization. A controversy exists regarding the use of the instrumentation in the tuberculous spine. METHODS: Retrospective case study and literature review. RESULTS: Because of the concomitant medical problems and little deterioration of the neurologic function, our patient is managed uneventfully with conservative treatment. CONCLUSION: To the authors' knowledge, this is an extremely rare reported complication of upper thoracic cage surgery for vertebral tuberculosis. This case demonstrates that the cage migration in the tuberculous spondylitis might have a rather benign clinical course and structural bone grafting or interbody cage insertion without supplemental instrument fixation seems to be inadequate.

Exacerbation of symptoms of lumbar disc herniation complicated by a schwannoma: a case report.

Herniation of the lumbar disc is a common cause of low back pain. Conservative management with physiotherapy, such as lumbar spine traction, is usually effective. Although a schwannoma of the lumbar spine is relatively uncommon, the clinical manifestations are similar to those of lumbar disc herniation, making the diagnosis difficult. This case report describes a 51-year-old male who had suffered from low back pain for 3 years and who was diagnosed with L2/L3 lumbar disc herniation. The low back pain was well-controlled by conservative treatment and the symptoms improved progressively. Two months prior to our evaluation, however, the symptoms worsened acutely, and were accompanied by the onset of symptoms of cauda equina syndrome. A small tumor at the site of the L2/L3 disc herniation, observed incidentally during magnetic resonance imaging, was responsible for the symptoms of spinal stenosis at the lumbar region. The patient underwent laminectomy, tumor resection, and discectomy with near-complete resolution of symptoms. In patients with lumbar disc herniation that improves with conservative treatment, the recurrence of symptoms should prompt a thorough review of the medical history, physical examination, and imaging studies to establish the diagnosis and prevent delay in treatment.