MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain.

Human acetyltransferases MOZ and MORF are implicated in chromosomal translocations associated with aggressive leukemias. Oncogenic translocations involve the far amino terminus of MOZ/MORF, the function of which remains unclear. Here, we identified and characterized two structured winged helix (WH) domains, WH1 and WH2, in MORF and MOZ. WHs bind DNA in a cooperative manner, with WH1 specifically recognizing unmethylated CpG sequences. Structural and genomic analyses show that the DNA binding function of WHs targets MORF/MOZ to gene promoters, stimulating transcription and H3K23 acetylation, and WH1 recruits oncogenic fusions to HOXA genes that trigger leukemogenesis. Cryo-EM, NMR, mass spectrometry and mutagenesis studies provide mechanistic insight into the DNA-binding mechanism, which includes the association of WH1 with the CpG-containing linker DNA and binding of WH2 to the dyad of the nucleosome. The discovery of WHs in MORF and MOZ and their DNA binding functions could open an avenue in developing therapeutics to treat diseases associated with aberrant MOZ/MORF acetyltransferase activities.

Efficacy and Safety of Percutaneous Ozone Injection Around Gasserian Ganglion for the Treatment of Trigeminal Neuralgia: A Multicenter Retrospective Study.

BACKGROUND: Ozone injection around Gasserian ganglion (OIAGG) has been reported to be an effective treatment for trigeminal neuralgia (TN); however, there remain areas for improvement. To overcome one of these limitations, a multicenter examination of application would be extremely helpful. OBJECTIVE: The goal of this report was to assess the efficacy of OIAGG for refractory TN across multiple centers and to explore factors predictive of successful treatment. DESIGN: A multicenter, retrospective study. SETTING: The study was conducted across 3 pain centers across China. PATIENTS AND METHODS: A total of 103 subjects from 3 pain centers were enrolled in the study. An ozone-oxygen mixture gas at a concentration of 30 µg/mL was injected into the area around the Gasserian ganglion performed under C-arm X-ray guidance. Primary outcome measures included a pain assessment using a visual analog scale (VAS) and the Barrow Neurological Institute (BNI) pain intensity scale. Clinical assessment of patients for these outcome measures was performed at pretreatment, post-treatment, 6 months, 1 year and 2 years after the OIAGG. RESULTS: Successful pain relief was defined as a score within BNI grades I-IIIa. The pain relief rates at post-treatment, 6 months, 1 year and 2 years after the procedure were 88.35%, 86.87%, 84.46% and 83.30%, respectively. The VAS at each observation time point was significantly different from the preoperative levels (P<0.05). Logistic regression analysis showed that previous nerve damage had a significant effect on the treatment results. No significant complications or side effects were found during or after treatment. CONCLUSION: This multicenter research confirms our previous single center results that OIAGG is both effective and safe for patients with TN.

Use of propofol for prevention of post-delivery nausea during cesarean section: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Nausea and vomiting are common, undesirable symptoms during cesarean section. We conducted this study to assess the antiemetic properties of propofol for the prevention and immediate treatment of post-delivery nausea and vomiting during cesarean section under combined spinal-epidural anesthesia. METHODS: Eighty women undergoing elective cesarean delivery under combined spinal-epidural anesthesia were randomized to receive either propofol at a plasma concentration of 1000 ng/mL or normal saline immediately after clamping of the umbilical cord. The incidence of post-delivery nausea and vomiting, patients requiring rescue antiemetic, bispectral index, sedation score, and the incidence of hypotension were assessed intraoperatively. Satisfaction and neonatal behavioral neurological assessments were evaluated postoperatively. RESULTS: The incidence of nausea was significantly lower in the propofol group compared to the placebo group (25% versus 60%, P < 0.001). The incidence of retching and vomiting showed no significant difference between the two groups. Propofol 20 mg as a rescue antiemetic was significantly effective in both the groups. Satisfaction level of patients and obstetricians in the propofol group was higher than in the placebo group. There was no statistical difference in the incidence of hypotension between the two groups both pre- and post-delivery. There was no difference in postoperative neonatal behavioral neurological assessment between groups. CONCLUSION: Propofol at a plasma concentration of 1000 ng/mL significantly reduced the incidence of post-delivery nausea compared to placebo, but had no effect on reducing retching or vomiting episodes during cesarean section.

Computed tomography-guided percutaneous ozone injection of the Gasserian ganglion for the treatment of trigeminal neuralgia.

OBJECTIVE: The aim of this study was to evaluate the therapeutic effect of computed tomography (CT)-guided percutaneous ozone injection for refractory trigeminal neuralgia. DESIGN: A retrospective evaluation was performed in the study. SETTING: The study was conducted at a university hospital pain center. PATIENTS AND METHODS: A total of 29 patients with a clinical diagnosis of refractory trigeminal neuralgia were enrolled. All patients were treated with a percutaneous ozone injection and one patient was excluded. There were 21 patients with classical trigeminal neuralgia (group A) and seven patients with painful trigeminal neuropathy caused by post-herpetic neuralgia (group B). The percutaneous injection was an oxygen-ozone mixture at an ozone concentration of 30 µg/mL into the Gasserian ganglion performed under CT guidance. The number of procedures performed varied from one to as many as 16. Outcomes were evaluated using visual analog scale (VAS) pain scores. RESULTS: The combined VAS scores were 7.11 ± 1.23 pretreatment, 2.86 ± 1.69 posttreatment (P < 0.05) and 3.25 ± 2.01 after 6-month follow-up (P < 0.05). In group A, the VAS scores were 7.10 ± 1.04 pretreatment and 2.90 ± 1.84 posttreatment (P < 0.05). In group B, the VAS scores were 7.14 ± 1.77 pretreatment and 2.71 ± 1.25 posttreatment (P < 0.05). After 6-months follow-up, the VAS score was 3.38 ± 2.18 in group A and 2.86 ± 1.46 in group B, a decrease compared to pretreatment (P < 0.05). VAS of Group A and B showed no difference not only in pretreatment but also in postreatment and follow-up. CONCLUSION: Percutaneous ozone injection is a safe and effective treatment for patients with refractory trigeminal neuralgia.

Cognitive effects of electro-acupuncture and pregabalin in a trigeminal neuralgia rat model induced by cobra venom.

OBJECTIVE: The objective of this study was to investigate the effects of electro-acupuncture (EA) and pregabalin on cognition impairment induced by chronic trigeminal neuralgia (TN) in rats. DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine and Critical Care Medicine, Aviation General Hospital of China Medical University. SUBJECTS: Forty adult male Sprague Dawley rats. METHODS: Rats were randomly divided into four groups. The TN model was induced by administration of cobra venom to the left infraorbital nerve. On postoperative day 14, either EA or pregabalin was administered, free behavioral activities were observed. Spatial learning and memory abilities were determined in the Morris water maze. The ultrastructural alterations of the Gasserian ganglion, medulla oblongata and hippocampus were examined by electron microscopy. The changes on long-term potentiation were investigated. RESULTS: After treatment, the exploratory behavior increased and the grooming behavior decreased (P<0.05) for the EA group and pregabalin group compared with the cobra venom group; moreover, demyelination of neurons in Gasserian ganglion and medulla oblongata was reversed. The number of platform site crossings, the average percentages of time in the target quadrant and the field excitatory postsynaptic potential slopes increased (P<0.05) in the EA group compared to the cobra venom group. However, the pregabalin group showed no differences compared to the cobra venom group (P>0.05). Vacuolar degeneration in the hippocampal neurons was mild in the EA group, while it was severe in the pregabalin group. CONCLUSION: EA and pregabalin could alleviate TN induced by cobra venom. EA could also inhibit the cognition deficit induced by TN, while pregabalin could not.