Coixendide efficacy in combination with temozolomide in glioblastoma and transcriptome analysis of the mechanism.

The purpose of this study was to explore the role of coixendide (Coix) combine with temozolomide (TMZ) in the treatment of Glioblastoma (GBM) and explore its possible mechanism. CCK-8 was used to determine the inhibitory rate of Coix group, TMZ group and drug combination group on GBM cells, and the combination index (CI) was calculated to determine whether they had synergistic effect. Then RNA was extracted from each group, transcriptome sequencing was performed, and differentially expressed genes (DEGs) were identified. The possible mechanism was analyzed by GO enrichment analysis and KEGG enrichment analysis. The CI of Coix and TMZ indicating a synergistic effect when TMZ concentration is 0.1 mg/ml and Coix concentration is 2 mg/ml. Transcriptome sequencing analysis showed that interferon (IFN) related genes were down-regulated by Coix and up-regulated by TMZ and combined drugs, however, the up-regulation induced by combined drugs was less than that of TMZ. Besides IFN related genes, cholesterol metabolism pathway were also been regulated. Coix and TMZ have synergistic effects in the treatment of GBM at certain doses. RNA-Seq results suggested that the abnormal on genetic materials caused by DNA damage induced by TMZ treatment can be sensed by IFN related genes and activates antiviral IFN signaling, causing the activation of repairing mechanism and drug resistance. Coix inhibits IFN related genes, thereby inhibits drug resistance of TMZ. In addition, the activation of ferroptosis and the regulation of DEGs in cholesterol metabolism pathway were also contributed to the synergistic effects of Coix and TMZ.

Parvalbumin neurons in the anterior nucleus of thalamus control absence seizures.

OBJECTIVE: Anterior nucleus of thalamus (ANT) has been widely accepted as a potential therapeutic target for drug-resistant epilepsy. Although increased volume of the ANT was also reported in patients with absence epilepsy, the relationship between the ANT and absence epilepsy has been barely illustrated. METHODS: Using chemogenetics, we evaluated the effect of ANT parvalbumin (PV) neurons on pentylenetetrazole (PTZ)-induced absence seizures in mice. RESULTS: We found that intraperitoneal injection of PTZ (30 mg/kg) can stably induce absence-like seizures characterized by bilaterally synchronous spike-wave discharges (SWDs). Selective activation of PV neurons in the ANT by chemogenetics could aggravate the severity of absence seizures, whereas selective inhibition of that cannot reverse this condition and even promote absence seizures as well. Moreover, chemogenetic inhibition of ANT PV neurons without administration of PTZ was also sufficient to generate SWDs. Analysis of background EEG showed that chemogenetic activation or inhibition of ANT PV neurons could both significantly increase the EEG power of delta oscillation in the frontal cortex, which might mediate the pro-seizure effect of ANT PV neurons. SIGNIFICANCE: Our findings indicated that either activation or inhibition of ANT PV neurons might disturb the intrinsic delta rhythms in the cortex and worsen absence seizures, which highlighted the importance of maintaining the activity of ANT PV neurons in absence seizure.

Life-threatening complications after microvascular decompression procedure: Lessons from a consecutive series of 596 patients.

The microvascular decompression procedure (MVD) is widely utilized on patients with neurovascular compression syndromes, such as trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia, which have failed medical therapy. However, surgical complications are an ongoing problem. We retrospectively reviewed a total of 596 patients undergoing MVD in the Affiliated Hospital of Qingdao University from January 2008 to December 2018. Furthermore, we discussed the cases with life-threatening complications to determine the potential causes, aiming to achieve the goal of safer microvascular decompression. There were seven cases with life-threatening complications. Of those complications, one was cerebellar infarction with acute hydrocephalus, one was infarction of the cerebellum and the brain stem with acute hydrocephalus and serious intracranial infection, two were cerebellar haematoma, one was multiple haemorrhage with acute hydrocephalus, one was supratentorial subdural haematoma, and one was cerebellar swelling with acute hydrocephalus. After therapy, one patient died, one was in a persistent vegetative state, and five were discharged from the hospital upon recovery. In brief, MVD is a safe operation, and life-threatening complications accompanying MVD are rare, but require attention. The causes of some life-threatening complications are still not completely clear. Surgeons should continuously improve surgical techniques and perioperative care to reduce potential risks.