Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1b is dramatically elevated in the serum of patients with non-small cell lung cancer (NSCLC). In vitro studies showed that IL-1b promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1b acted through the COX2-HIF1a pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1b upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1b-mediated repression of miR-101 and IL-1b-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1b-miR-101-Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC. Cancer Res; 74(17); 4720-30. Ó2014 AACR.

Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage in improving MIRI. But the regulatory effect and mechanism of NAR on ferroptosis in MIRI have not been reported. After the rats were given NAR and induced to form myocardial ischemia-reperfusion (MI/R) injury, Tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats, and Hematoxylin-eosin (H&E) staining was used to detect myocardial injury. The markers of tissue inflammation were detected by ELISA. Serum creatine kinase Serum creatin kinase (CPK), Lactate dehydrogenase (LDH), and lipid peroxide (LPO) and oxidative stress related levels were measured. In addition, iron detection kits were used to detect total iron and Fe 2+ levels in cardiac tissues, and western blot was used to detect the expression of ferroptosis-related proteins and the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). At the cellular level, H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and ferroptosis inducer Erastin was administered to detect cell viability, ferroptosis-related indicators, oxidative stress related indicators, and expressions of Nrf2 and GPX4, to explore the mechanisms involved. NAR alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc – /GPX4 axis and improved ferroptosis. At the cellular level, ferroptosis inducer Erastin reversed the protective effect of NAR on H/R-induced H9C2 cardiomyocytes. In conclusion, NAR can alleviate MIRI by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis.

Background: Spontaneous intraventricular hemorrhage is an infrequent but severe complication of hemorrhagic stroke. The conventional treatment of intraventricular hemorrhage consists of ventricular drainage or surgical evacuation, but neither of them is encouraged. The objective of this article is to compare different surgical procedures in order to evaluate a method of minimally invasive treatment for intraventricular hemorrhage. Methods: Neuroendoscopy was applied to treat 22 cases of intraventricular hemorrhage. Twenty cases of the same disease that were treated by external ventricular drainage were taken as a control and comparison. Results: All patients were followed up for 2 months. In the neuroendoscopy group, according to the Glasgow outcome scale, the result was excellent in 5 cases, good in 9, fair in 4, poor in 2 and death in 2. In the external ventricular drainage group, the result was excellent in 1 case, good in 5, fair in 7, poor in 5 and death in 2. More patients in the neuroendoscopy group showed good recovery after 2 months of surgery (p < 0.05). The difference in mortality rate between the 2 groups was not statistically significant (p > 0.05). Conclusions: Neuroendoscopic neurosurgery for intraventricular hemorrhage offers better surgical treatment because it is characterized by visualized manipulation, effective hemorrhage evacuation and excellent postoperative outcomes.

Deep brain stimulation (DBS) is an established treatment for patients with Parkinson’s disease (PD). Sleep disorders are common complications of PD and affected by subthalamic DBS treatment. To achieve more precise neuromodulation, chronic sleep monitoring and closed-loop DBS toward sleep-wake cycles could potentially be utilized. Local field potential (LFP) signals that are sensed by the DBS electrode could be processed as primary feedback signals. This is the first study to systematically investigate the sleep-stage classification based on LFPs in subthalamic nucleus (STN). With our newly developed recording and transmission system, STN-LFPs were collected from 12 PD patients during wakefulness and nocturnal polysomnography sleep monitoring at one month after DBS implantation. Automatic sleep-stage classification models were built with robust and interpretable machine learning methods (support vector machine and decision tree). The accuracy, sensitivity, selectivity, and specificity of the classification reached high values (above 90% at most measures) at group and individual levels. Features extracted in alpha (8–13 Hz), beta (13–35 Hz), and gamma (35–50 Hz) bands were found to contribute the most to the classification. These results will directly guide the engineering development of implantable sleep monitoring and closed-loop DBS and pave the way for a better understanding of the STN-LFP sleep patterns.

Objective: Current understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large-scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS-induced activity at the whole-brain level. Using a novel 3T magnetic resonance imaging (MRI)-compatible stimulator, we investigated whole-brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease. Methods: Fourteen patients received STN-DBS treatment and participated in a block-design functional MRI (fMRI) experiment, wherein stimulations were delivered during "ON" blocks interleaved with "OFF" blocks. fMRI responses to low-frequency (60Hz) and high-frequency(130Hz) STN-DBS were measured 1, 3, 6, and 12 months postsurgery. To ensure reliability, multiple runs (48 minutes) of fMRI data were acquired at each postsurgical visit. Presurgical resting-state fMRI (30 minutes) data were also acquired. Results: Two neurocircuits showed highly replicable, but distinct responses to STN-DBS. A circuit involving the globus pallidus internus (GPi), thalamus, and deep cerebellar nuclei was significantly activated, whereas another circuit involving the primary motor cortex (M1), putamen, and cerebellum showed DBS-induced deactivation. These 2 circuits were dissociable in terms of their DBS-induced responses and resting-state functional connectivity. The GPi circuit was frequency-dependent, selectively responding to high-frequency stimulation, whereas the M1 circuit was responsive in a time-dependent manner, showing enhanced deactivation over time. Finally, activation of the GPi circuit was associated with overall motor improvement, whereas M1 circuit deactivation was related to reduced bradykinesia. Interpretation: Concurrent DBS-fMRI using 3T revealed 2 distinct circuits that responded differentially to STN-DBS and were related to divergent symptoms, a finding that may provide novel insights into the neural mechanisms underlying DBS.

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Glioblastoma multiforme (GBM) is a type of malignant carcinoma found in the brain. Its high frequency of occurrence and poor survival rate have garnered much research attention in recent years. Long non-coding RNAs (lncRNAs) are known to be related to the formation and progression of several cancer types by both promoting and suppressing tumor transformation. H19 is one such lncRNA and has been shown to be upregulated in a few types of cancer. In this study, we discovered that the expression of H19 increased in GBM cell lines. H19 knocked down GBM cells also displayed decreased cellular proliferation and a higher apoptosis rate when induced by temozolomide. Interestingly, the GBM cell lines U87MG and U251 were found to express cancer stem cell markers CD133, NANOG, Oct4 and Sox2. Expression of these markers was downregulated in H19-deficient cells. Collectively, these data suggest a role for H19 in contributing to GBM malignancy and the maintenance of its stem cell properties.

Glioblastoma pathogenesis is related to multiple processes that affected by dozens of regulatory factors, but the potential underlying factors regulating glioblastoma progression remains unclear. The goal of this research was to determine how the ribonucleotide reductase M2 subunit (RRM2) influenced proliferation, invasion, migration, and apoptosis of human glioblastoma cells. The level of proliferation of human glioblastoma cells was measured through CCK8, colony formation assay and immunofluorescence stains. Flow cytometry (FCM), wound healing, and transwell assays were conducted to detect cell apoptosis, migration, and invasion. Apoptotic level of cells and invasion-related expression of protein were measured by Western blot. Xenograft tumor model was established to confirm effect of RRM2 on the proliferation of human glioblastoma cells in vivo. Silencing RRM2 inhibited proliferation, invasion, and migration of glioblastoma cells whereas enhanced apoptosis rate. Overexpressing RRM2 promoted proliferation, migration and invasion but suppressed apoptosis. In vivo, Overexpressing RRM2 accelerated the tumor growth in glioblastoma cells. The present study illustrated that RRM2 was overexpressed in human glioblastoma cells. RRM2 promoted proliferation, migration, and invasion but inhibited apoptosis of human glioblastoma cells.