Independent association of the Meckel's cave with trigeminal neuralgia and development of a screening tool.

PURPOSE: To 1) investigate the association of the properties of the Meckel's cave (MC) with TN occurrence (i.e., affected vs. unaffected nerves) and whether such association was independent of neurovascular contact (NVC); and 2) develop an objective screening tool for TN. MATERIALS AND METHODS: Two hundred and nineteen trigeminal nerves were included. (The severity of) NVC was identified for individual nerve, and a set of 107 radiomic features were extracted to characterize various properties of each MC. Both procedures were primarily based on magnetic resonance imaging sequences. A radiomic score (Rad-score) was constructed for each MC to integrate the features associated with TN occurrence. Independent t-test and logistic regression were conducted to assess the association and develop the screening tool mentioned above. RESULTS: Twelve features were selected to build the Rad-score, with the Inverse Difference Moment Normalized (IDMN) having the greatest weight. The Rad-score was significantly (p ≤ 0.05) higher in the affected compared to the unaffected nerves, irrespective of NVC. The Rad-score and NVC were incorporated in the regression model/screening tool, which demonstrated an acceptable discriminating ability (C-statistic = 0.84). CONCLUSION: This study has identified a potential association of the properties/features of the MC with TN occurrence, probably involving the demyelination and axonal injury of the trigeminal ganglion within the MC as suggested by the IDMN. Such association may be independent of NVC. This finding may provide new insight into the etiology and/or pathophysiology of TN. The screening tool, which demonstrated an acceptable discriminating ability, may contribute to an improvement in its diagnosis.

[Retracted] MicroRNA­21 promotes migration and invasion of glioma cells via activation of Sox2 and ß­catenin signaling.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that there were several data panels showing the results of Transwell migration and invasion assay experiments in Figs. 1A and 2A that contained overlapping sections of data, such that these data, which were intended to have shown the results from differently performed experiments, appeared to have been derived from a smaller number of original sources. Furthermore, the data panels shown in Fig. 3A for the 'Control/U343' and 'Control/172', and the 'miR­21/ß­catenin' and 'Control/T98', experiments were also found to be unexpectedly similar, given that these were likewise intended to show the results from differently performed experiments. After having conducted an independent investigation in the Editorial Office, the Editor of Molecular Medicine Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [Molecular Medicine Reports 15: 187­193, 2017; DOI: 10.3892/mmr.2016.5971].

Significance of different offending vessels and development of a potential screening tool for trigeminal neuralgia.

OBJECTIVES: This study was performed amongst trigeminal neuralgia (TN) patients with neurovascular contact (NVC) to 1) investigate the association of the demographic and radiologic factors/variables with TN occurrence, and 2) develop a screening tool for TN/TN-affected nerves based on the factors/variables associated with it. METHODS: Eighty-five TN patients were recruited, and 121 trigeminal nerves with NVC were derived from them. Based on MRI sequences, including balanced turbo field echo and enhanced T1 high-resolution isotropic volume excitation, radiologic factors/variables for each nerve, from the offending vessel to the presence of nerve displacement, were identified by a neuroradiologist and a neurosurgeon. Demographic and clinical data were obtained from clinical notes. Logistic regression was performed to assess the association of the factors/variables with TN occurrence (i.e., affected vs. unaffected nerves). RESULTS: Three factors/variables were significantly (p < 0.05) associated with TN occurrence amongst patients with NVC: nerve laterality, vertebral artery (VA) involvement, and the presence of nerve displacement. The nerves with VA involvement, those on the right side, and those with nerve displacement exhibited a significantly higher likelihood/odd of being affected by TN, compared to those without VA involvement, those on the left side, and those without nerve displacement, respectively. Based on these factors/variables, a screening tool/nomogram with acceptable accuracy was established (C-statistic/AUC = 0.80). CONCLUSIONS: This study revealed an association of the three radiologic factors/variables with TN occurrence. A screening tool for TN/TN-affected nerves was established based on them. The findings may lay a foundation for an improvement of the diagnosis and clinical management of TN. KEY POINTS: • VA involvement and nerve displacement could be identified using MRI, and are significantly associated with TN occurrence. • A potential objective screening tool/nomogram for TN/TN-affected nerves could be established based on the three radiologic factors/variables: VA involvement, the presence of nerve displacement, and nerve laterality. • The screening accuracy of the tool/nomogram is acceptable as the C-statistic is 0.80.

Cerebral perfusion alterations in patients with trigeminal neuralgia as measured by pseudo-continuous arterial spin labeling.

Background: Accumulating evidence suggests that trigeminal neuralgia (TN) causes structural and functional alterations in the brain. However, only a few studies have focused on cerebral blood flow (CBF) changes in patients with TN. This study aimed to explore whether altered cerebral perfusion patterns exist in patients with TN and investigate the relationship between abnormal regional CBF (rCBF) and clinical characteristics of TN. Materials and methods: This study included 28 patients with TN and 30 age- and sex-matched healthy controls (HCs) who underwent perfusion functional MRI (fMRI) of the brain using pseudo-continuous arterial spin labeling (pCASL) in the resting state. The regions of significantly altered CBF in patients with TN were detected using group comparison analyses. Then, the relationships between the clinical characteristics and abnormal rCBF were further investigated. Results: Compared to the control group, patients with TN exhibited increased rCBF, primarily in the thalamus, middle frontal gyrus (MFG), and left insula. Furthermore, the CBF values of the thalamus were negatively correlated with the pain intensity of TN and positively correlated with pain duration in patients with TN. Conclusion: Primary alterations in rCBF in patients with TN occurred in different brain regions related to pain, which are involved in cognitive-affective interaction, pain perception, and pain modulation. These results indicate that non-invasive resting cerebral perfusion imaging may contribute complementary information to further understanding the neuropathological mechanism underlying TN.

Flatness of the Meckel cave may cause primary trigeminal neuralgia: a radiomics-based study.

BACKGROUND: Neurovascular contact (NVC) is the main cause of primary trigeminal neuralgia (PTN); however, cases of PTN without NVC are still observed. In this study, the Meckel cave (MC) morphology in PTN were analyzed by radiomics and compared to healthy controls (HCs) to explore the cause of PTN. METHODS: We studied the 3.0T MRI data of 115 patients with PTN and 46 HCs. Bilateral MC was modeled using the 3D Slicer software, and the morphological characteristics of MC were analyzed using the radiomics method. RESULTS: The right side incidence rate in the PTN group was higher than the left side incidence. By analyzing the flatness feature of MC, we observed that the affected side of the PTN was lower than that of the unaffected side, the right MC of the PTN and HC was lower than that of the left MC, the MC of the affected side of the left and right PTN without bilateral NVC was lower than that of the unaffected side. CONCLUSIONS: By providing a method to analyze the morphology of the MC, we found that there is an asymmetry in the morphology of bilateral MC in the PTN and HC groups. It can be inferred that the flatness of the MC may be a cause of PTN.

Cortical thickness, gyrification and sulcal depth in trigeminal neuralgia.

Neuroimaging studies have documented brain structural alterations induced by chronic pain, particularly in gray matter volume. However, the effects of trigeminal neuralgia (TN), a severe paroxysmal pain disorder, on cortical morphology are not yet known. In this study, we recruited 30 TN patients and 30 age-, and gender-matched healthy controls (HCs). Using Computational Anatomy Toolbox (CAT12), we calculated and compared group differences in cortical thickness, gyrification, and sulcal depth with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between altered cortical characteristics and pain intensity were investigated with correlation analysis. Compared to HCs, TN patients exhibited significantly decreased cortical thickness in the left inferior frontal, and left medial orbitofrontal cortex; decreased gyrification in the left superior frontal cortex; and decreased sulcal depth in the bilateral superior frontal (extending to anterior cingulate) cortex. In addition, we found significantly negative correlations between the mean cortical thickness in left medial orbitofrontal cortex and pain intensity, and between the mean gyrification in left superior frontal cortex and pain intensity. Chronic pain may be associated with abnormal cortical thickness, gyrification and sulcal depth in trigeminal neuralgia. These morphological changes might contribute to understand the underlying neurobiological mechanism of trigeminal neuralgia.

DeepBindPoc: a deep learning method to rank ligand binding pockets using molecular vector representation.

Accurate identification of ligand-binding pockets in a protein is important for structure-based drug design. In recent years, several deep learning models were developed to learn important physical-chemical and spatial information to predict ligand-binding pockets in a protein. However, ranking the native ligand binding pockets from a pool of predicted pockets is still a hard task for computational molecular biologists using a single web-based tool. Hence, we believe, by using closer to real application data set as training and by providing ligand information, an enhanced model to identify accurate pockets can be obtained. In this article, we propose a new deep learning method called DeepBindPoc for identifying and ranking ligand-binding pockets in proteins. The model is built by using information about the binding pocket and associated ligand. We take advantage of the mol2vec tool to represent both the given ligand and pocket as vectors to construct a densely fully connected layer model. During the training, important features for pocket-ligand binding are automatically extracted and high-level information is preserved appropriately. DeepBindPoc demonstrated a strong complementary advantage for the detection of native-like pockets when combined with traditional popular methods, such as fpocket and P2Rank. The proposed method is extensively tested and validated with standard procedures on multiple datasets, including a dataset with G-protein Coupled receptors. The systematic testing and validation of our method suggest that DeepBindPoc is a valuable tool to rank near-native pockets for theoretically modeled protein with unknown experimental active site but have known ligand. The DeepBindPoc model described in this article is available at GitHub (https://github.com/haiping1010/DeepBindPoc) and the webserver is available at (http://cbblab.siat.ac.cn/DeepBindPoc/index.php).

Preoperative Imaging and Microscopic Navigation During Surgery Can Avoid Unnecessarily Opening the Mastoid Air Cells Through Craniotomy Using the Retrosigmoid Approach.

OBJECTIVE: To analyze treatment of microvascular decompression using the retrosigmoid approach (RA) in primary trigeminal neuralgia and hemifacial spasm using preoperative images combined with intraoperative microscopic navigation to avoid unnecessarily opening the mastoid air cells (MACs). METHODS: Ten patients with primary trigeminal neuralgia and 20 patients with hemifacial spasm (test group) were treated using RA for microvascular decompression. Preoperative head magnetic resonance angiography and temporal bone computed tomography were performed and the images registered using SPM12 and fused with MRIcron to determine the relationship between MACs and sigmoid sinuses. An O-arm was used for navigation, and the transverse sigmoid sinus was projected under a microscope to guide RA. A control group comprised 139 patients who had the same surgical procedure as the test group but without image processing or intraoperative navigation. RESULTS: The relationship between MACs and the ipsilateral sigmoid sinus was classified as follows: I, MACs did not exceed the lateral edge of the ipsilateral sigmoid sinus (10/60); II, MACs exceeded the ipsilateral lateral edge of the sigmoid sinus but did not exceed the medial edge (42/60); and III, MACs exceeded the medial edge of the ipsilateral sigmoid sinus (8/60). Test and control groups showed significant differences in the incidences of opening MACs (P = 0.003). There was no cerebrospinal fluid leakage or scalp and intracranial infection at follow-up. CONCLUSIONS: Image processing and intraoperative microscopic navigation can avoid unnecessarily opening MACs and might reduce postoperative cerebrospinal leakage and scalp infection after RA craniotomy.

miR-135a-5p and miR-124-3p Inhibit Malignancy of Glioblastoma by Downregulation of Syndecan Binding Protein.

Due to its high invasiveness, glioblastoma is difficult to treat by surgery, radiotherapy, chemotherapy or any combination therapy. Syndecan binding protein (SDCBP), a widely distributed intracellular scaffold protein, has an important role in both physiological and pathological process. In the current work, we have identified target sequences for miR-135a-5p and miR-124-3p in the 3'-untranslated region of the SDCBP mRNA. Therefore, we have investigated the relationship between SDCBP, miR-135a-5p and miR-124-3p in glioblastoma multiforme cells T98G and U87 in vitro and in vivo. Dual luciferase activity assay documented that SDCBP is, in fact, the target of miR-135a-5p, miR-124-3. Western blot, qRT-PCR, proliferation, migration, and invasion assays have demonstrated that of silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p significantly interferes with the malignant properties of glioblastoma cells. In vivo studies have shown that silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p result in a marked decrease of tumor size and prolong life of tumor-bearing mice. A therapy combining the three treatments inhibits synergistically subcutaneous tumor growth in nude mice. In conclusion, proliferation, migration and invasion of glioblastoma can be inhibited by targeted regulation of SDCBP through upregulation of miR-135a-5p and miR-124-3p.

MicroRNA­21 promotes migration and invasion of glioma cells via activation of Sox2 and ß­catenin signaling.

The expression of microRNA 21 (miR-21) has been reported to be upregulated in various types of cancer, including malignant gliomas. However, its functions and mechanisms in glioma remain to be fully elucidated. The present study established miRNA­21 overexpression and knockdown cell lines using SRY­box 2 (Sox2) small interfering RNA (siRNA) to knockdown expression and Sox2 cDNA was cloned into pcDNA 3.1 mammalian expression vector for ectopic expression. BIO and XAV­939 were used for ß­catenin signaling activation and knockdown, respectively. Transwell chambers were used to assay the capacity of cells to migrate. The present study determined that increased expression of miR­21 significantly promoted the migration and invasion of glioma cells, which was accompanied by an upregulated expression of the Sox2 protein. Sox2 overexpression also promoted glioma cell migration and invasion, whereas Sox2 siRNA markedly reduced the miR­21­enhanced migration and invasion of glioma cells, indicating Sox2 may act as a crucial mediator of miR­21 function. Furthermore, miR­21 also upregulated the protein expression level of ß­catenin, whereas anti­miR­21 and Sox2 knockdown significantly reduced ß­catenin expression. BIO, a ß­catenin specific agonist, enhanced migration and invasion of glioma cells. XAV­939, an inhibitor of ß­catenin signaling, markedly inhibited the migration and invasion of glioma cells, suggesting that ß­catenin may be associated with miR­21­ and Sox2­induced invasion of glioma cells. Notably, BIO restored the migration and invasion potential of glioma cells, which were inhibited by Sox2 siRNA and anti­miR­21. These findings indicated that ß­catenin may be an important downstream mediator of miR­21 and Sox2. Therefore, the present study identified the miR­21/Sox2/ß­catenin signaling pathway, which may regulate the migration and invasion of human glioma cells.