Squamocin modulates histone H3 phosphorylation levels and induces G1 phase arrest and apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>Histone modifications in tumorigenesis are increasingly recognized as important epigenetic factors leading to cancer. Increased phosphorylation levels of histone H3 as a result of aurora B and pMSK1 overexpression were observed in various tumors. We selected <it>aurora B </it>and <it>MSK1 </it>as representatives for testing various compounds and drugs, and found that squamocin, a bis-tetrahydrofuran annonaceous acetogenin, exerted a potent effect on histone H3 phosphorylation.</p> <p>Methods</p> <p>GBM8401, Huh-7, and SW620 cells were incubated with 15, 30, and 60 μM squamocin for 24 h. The expressions of mRNA and proteins were analyzed by qRT-PCR and Western blotting, respectively. The cell viability was determined by an MTT assay. Cell cycle distribution and apoptotic cells were analyzed by flow cytometry.</p> <p>Results</p> <p>Our results showed that squamocin inhibited the proliferation of GBM8401, Huh-7, and SW620 cells, arrested the cell cycle at the G₁phase, and activated both intrinsic and extrinsic pathways to apoptosis. In addition, we demonstrated that squamocin had the ability to modulate the phosphorylation levels of H3S10 (H3S10p) and H3S28 (H3S28p) in association with the downregulation of aurora B and pMSK1 expressions.</p> <p>Conclusions</p> <p>This study is the first to show that squamocin affects epigenetic alterations by modulating histone H3 phosphorylation at S10 and S28, providing a novel view of the antitumor mechanism of squamocin.</p

Subthalamic nucleus deep brain stimulation in elderly patients – analysis of outcome and complications

BACKGROUND: There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. METHODS: Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age ≥ 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. RESULTS: Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. CONCLUSION: DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate

Behavioral Disorders in Association with Posterior Callosal and Frontal Cerebral Infarction

Behavioral disorders were a prominent clinical feature after the surgical treatment of an anterior communicating artery aneurysm rupture in a 44-year-old man. Callosal apraxia was associated with an alien hand. The latter remained 1 year after surgery while diagonistic apraxia disappeared after 3 months. Other callosal signs included left agraphia, tactile anomia and auditory suppression. MRI revealed posterior callosal infarction and a right frontal infarct. The association of diagonistic apraxia and alien hand is rarely reported

Behavioral Disorders in Association with Posterior Callosal and Frontal Cerebral Infarction

Behavioral disorders were a prominent clinical feature after the surgical treatment of an anterior communicating artery aneurysm rupture in a 44-year-old man. Callosal apraxia was associated with an alien hand. The latter remained 1 year after surgery while diagonistic apraxia disappeared after 3 months. Other callosal signs included left agraphia, tactile anomia and auditory suppression. MRI revealed posterior callosal infarction and a right frontal infarct. The association of diagonistic apraxia and alien hand is rarely reported

Hippocampal Microbleed on a Post-Mortem T2*-Weighted Gradient-Echo 7.0-Tesla Magnetic Resonance Imaging

The present post-mortem study of a brain from an Alzheimer patient showed on a T2*-weighted gradient-echo 7.0-T MRI of a coronal brain section a hyposignal in the hippocampus, suggesting a microbleed. On the corresponding histological examination, only iron deposits around the granular cellular layer and in blood vessel walls of the hippocampus were observed without evidence of a bleeding. This case report illustrates that the detection of microbleeds on MRI has to be interpreted with caution