Sedanolide Activates KEAP1-NRF2 Pathway and Ameliorates Hydrogen Peroxide-Induced Apoptotic Cell Death.

Sedanolide is a bioactive compound with anti-inflammatory and antitumor activities. Although it has been recently suggested that sedanolide activates the nuclear factor E2-related factor 2 (NRF2) pathway, there is little research on its effects on cellular resistance to oxidative stress. The objective of the present study was to investigate the function of sedanolide in suppressing hydrogen peroxide (H2O2)-induced oxidative damage and the underlying molecular mechanisms in human hepatoblastoma cell line HepG2 cells. We found that sedanolide activated the antioxidant response element (ARE)-dependent transcription mediated by the nuclear translocation of NRF2. Pathway enrichment analysis of RNA sequencing data revealed that sedanolide upregulated the transcription of antioxidant enzymes involved in the NRF2 pathway and glutathione metabolism. Then, we further investigated whether sedanolide exerts cytoprotective effects against H2O2-induced cell death. We showed that sedanolide significantly attenuated cytosolic and mitochondrial reactive oxygen species (ROS) generation induced by exposure to H2O2. Furthermore, we demonstrated that pretreatment with sedanolide conferred a significant cytoprotective effect against H2O2-induced cell death probably due to preventing the decrease in the mitochondrial membrane potential and the increase in caspase-3/7 activity. Our study demonstrated that sedanolide enhanced cellular resistance to oxidative damage via the activation of the Kelch-like ECH-associated protein 1 (KEAP1)-NRF2 pathway.

[Sequential changes in inflammatory and stress responses during 24-hour running].

Running for an extended period of time can cause severe stress on the body, subsequently damaging skeletal muscle and resulting in changes in blood components. However, few reports have examined vital responses during and after running. This study analyzed inflammatory responses during and after running and changes in stress responses as determined by serial changes in blood components. Venous blood was obtained before starting, 6 h after starting, 12 h after starting, and immediately after finishing 24 h of continuous running. Samples were analyzed for high-sensitivity C-reactive protein (hsCRP), pentraxin 3 (ptx3), white blood cells (WBC), myoglobin, creatine kinase (CK), and hormones. Diet and physical activity were standardized 24 h before and after running. Subjects comprised 16 men who agreed to participate in experimental running on November 8 and 9, 2008, at Tokyo Gakugei University. Mean running distance was 151.32 +/- 32.1 km (range, 83.6-210.0 km) in 24 h. A significant increase in hsCRP was seen from 12 h after starting to completion. Compared to hsCRP, ptx3 gradually increased from before starting to after completion, showing a significant difference between pre and post-run ptx3 levels. WBC count increased significantly until 6 h after starting. Neutrophils in leukocytosis increased significantly during the first 6 h. Eosinophils decreased significantly over the course of the 24 h. Cortisol increased, and testosterone decreased significantly from 6 h after starting. Dehydroepiandrosterone sulfate (DHEA-S), myoglobin, and CK increased over the course of the 24 h. Reactive oxygen metabolites (d-ROMs) changed within the normal range though there was a significant decrease, and biological anti-oxidant potential (BAP) stabilized. Active natural killer cells decreased significantly after 24 h running. Biopyrrin (BPn) increased significantly. Changes in stress oxide were small both during and after running, and adaptation for antioxidation was good. DHEAS, a biomarker of aging, was found to increase over the course of the 24 h, suggesting that controlling decreases in DHEA-S may be possible using exercise, particularly in males. The key finding was that DHEA S levels tended to increase with continuous aerobic exercise.

Parent artery occlusion for ruptured "true" posterior communicating artery aneurysm.

A case of a patient with a ruptured true posterior communicating artery (PCoA) aneurysm is reported, who had been managed by early endovascular parent artery occlusion with coils. The small blister aneurysm was located at the proximal PCoA itself and directed superiorly. Postoperative course was uneventful. During 1-month follow-up, the patient recovered well and could care for herself. Aneurysms of the PCoA itself are very rare. As reported to date, surgical procedures would favor microsurgical clipping over endovascular coil embolization. Endovascular treatment may be a good alternative to surgical trapping for true PCoA blister aneurysm.

A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children.

BACKGROUND: Long-course prednisolone regimens have been shown to be more effective than short-course regimens in sustaining remission of nephrotic syndrome in children. However, the most beneficial approach among the long-course regimens remains unknown. METHODS: Seventy-three children with new-onset nephrotic syndrome were allocated at random to the two long-course regimens and followed up for 2 years. Group A was administered prednisolone at a daily dose of 60 mg/m2 for 6 weeks, followed by an alternate-day dose of 40 mg/m2 for 6 weeks (the long daily regimen). Group B was administered the same daily dose for 4 weeks, followed by an alternate-day dose of 60 mg/m2 for 4 weeks, and doses were tapered by 10 mg/m2 every 4 weeks (the long alternate-day regimen). RESULTS: Group B had a lower incidence of corticosteroid toxicities than group A during the initial treatment. Kaplan-Meier analysis of the sustained remission rate of the two treatment groups showed a marginally significant difference (P = 0.069) and showed a significant difference when patients were stratified for age of disease onset (P = 0.048). In a subgroup of younger children (<4 years at onset), group B had a greater rate of sustained remission (P < 0.01) and fewer children with frequent relapses (P < 0.05) than group A, whereas in older children (> or =4 years at onset), both groups had similar good sustained remission rates. CONCLUSION: These findings collectively indicate that the long alternate-day regimen may be more beneficial, with less corticosteroid toxicities, than the long daily regimen, and children with younger age at disease onset may be susceptible to relapse and especially benefit from the long alternate-day regimen for sustaining remission of the disease.

[Reversible posterior leukoencephalopathy syndrome: experience in 3 cases].

We report 3 cases with reversible posterior leukoencephalopathy syndrome (RPLS) accompanied by eclampsia or hypertensive encephalopathy. RPLS may develop in patients who have eclampsia or hypertensive encephalopathy or who are immunosuppressed. The findings on neuroimaging are characteristic of subcortical edema without infarction. A 27-year-old primigravida developed eclampsia at 37 weeks of gestation. MRI was performed 4 hours after the onset. The FLAIR sequence delineated extensive hyperintense lesions in the temporal and occipital lobe bilaterally. MR angiography(MRA) performed 6 days after the onset of symptoms clearly demonstrated intracranial vasospasm. Follow up MRI and MRA were performed 3 weeks after the onset. The MRI showed slight residual hyperintensity in the occipital lobe. The MRA showed the disappearance of the vasospasm. A 39-year-old woman on the 8th postpartum day presented with thunderclap headache, which led to a search for SAH. She visited our hospital, whose high arterial blood pressure (220/110 mmHg) was observed. Both CT and MRA were normal. MRI revealed abnormalities in the parieto-occipital regions bilaterally. Treatment of hypertension led to resolution of the posterior leukoencephalopathy. A 38-year-old woman on the 11th postpartum day suddenly developed vertigo, visual disturbance and generalized convulsion. MRI was performed 7 days after the onset. The FLAIR sequence delineated extensive hyperintense lesions in the occipital lobe bilaterally. MRA clearly demonstrated diffuse intracranial vasospasm. MRA performed 3 weeks after the onset showed the disappearance of the vasospasm. In conclusion, our experience suggests that the MRI and MRA noninvasively provide valuable findings which are complementary in the diagnosis and follow-up examination of a brain edema and vasospasm in RPLS.

Cyclosporin A treatment for membranoproliferative glomerulonephritis type II.

A nephrotic patient with membranoproliferative glomerulonephritis type II (MPGN II) was treated with cyclosporin A (CSA) and alternate-day low-dose prednisolone. This patient developed the nephrotic syndrome twice. The second episode of the nephrotic syndrome was steroid resistant, and therefore this patient was treated with a CSA regimen. During treatments with alternate-day low-dose prednisolone and CSA, this patient recovered from the nephrotic syndrome. We conclude that CSA therapy may be effective for patients with the steroid-resistant nephrotic syndrome caused by MPGN II.