Unveiling Mechanical Activation: GAIN Domain Unfolding and Dissociation in Adhesion GPCRs.

Adhesion G protein-coupled receptors (aGPCRs) have extracellular regions (ECRs) containing GPCR autoproteolysis-inducing (GAIN) domains. The GAIN domain enables the ECR to self-cleave into N- and C-terminal fragments. However, the impact of force on the GAIN domain's conformation, critical for mechanosensitive aGPCR activation, remains unclear. Our study investigated the mechanical stability of GAIN domains in three aGPCRs (B, G, and L subfamilies) at a loading rate of 1 pN/s. We discovered that forces of a few piconewtons can destabilize the GAIN domains. In autocleaved aGPCRs ADGRG1/GPR56 and ADGRL1/LPHN1, these forces cause the GAIN domain detachment from the membrane-proximal Stachel sequence, preceded by partial unfolding. In noncleavable aGPCR ADGRB3/BAI3 and cleavage-deficient mutant ADGRG1/GPR56-T383G, complex mechanical unfolding of the GAIN domain occurs. Additionally, GAIN domain detachment happens during cell migration. Our findings support the mechanical activation hypothesis of aGPCRs, emphasizing the sensitivity of the GAIN domain structure and detachment to physiological force ranges.

ARRDC3 polymorphisms may affect the risk of glioma in Chinese Han.

This study ascertained to explore the potential contribution of ARRDC3 polymorphisms in the risk and prognosis of glioma. One thousand sixty-one patients and healthy controls were conducted to assess whether ARDC3 polymorphism was associated with glioma risk and prognosis. Four sites in ARRDC3 were selected and genotyped in MassARRAY platform. The calculated odd ratios and 95% confidence intervals from logistic regression were applied for risk assessment. The relationship between ARRDC3 variants and glioma prognosis was evaluated using log-rank test, Kaplan-Meier analysis, and so on. Also, false-positive report probability (FPRP) and statistical power were also assessed. Our findings suggested the negative role of ARRDC3 polymorphisms in the glioma risk. We also found the effect of candidate SNPs in ARRDC3 on the susceptibility to glioma was dependent on the age, gender, and histology of glioma patients. The results suggested that the genetic polymorphisms of ARRDC3 were related to an increased risk of glioma.

Prognostic Potential of METTL7B in Glioma.

OBJECTIVE: Methyltransferase-like 7B (METTL7B) is a member of methyltransferase-like family. Little is known about the exact role of METTL7B in cancer. This study aims to investigate the role of METTL7B in gliomas. METHODS: The expression of METTL7B in glioma and adjacent normal tissues were examined by using TCGA, Chinese Glioma Genome Atlas (CGGA) database, and clinical tissues. RESULTS: The results showed that METTL7B was highly expressed in glioma. Patients with high levels of METTL7B usually had poor survival in glioma, especially in low-grade glioma (LGG). Data from CGGA showed that METTL7B was an independent risk factor of glioma and can be used to evaluate the survival time of glioma patients. Hypomethylation in the METTL7B CpG islands was lower in LGG, and all the hypomethylated METTL7B islands were correlated with poor LGG survival. Furthermore, METTL7B levels were correlated with high numbers of tumor infiltrated immune cells in glioma, especially in LGG. ). Gene Set Enrichment Analysis found METTL7B was correlated with leukocyte proliferation, T-cell proliferation, peptidase activity, lymphocyte activation, etc. TCGA and CGGA database analysis showed that there were 1,546 and 1,117 genes that had a synergistic effect with METTL7B in glioma, respectively, and there were 372 genes overlapped between the 2 groups, including PD-L1. Data from clinical tissues also showed PD-L1 was highly expressed in glioma tissues and was positively correlated with METTL7B. CONCLUSION: Our study suggested that METTL7B was a potential prognostic biomarker for glioma and other cancers, and it may act as an oncogenic driver and may be a potential therapeutic target in human cancer, especially in LGG.

miR-452-3p Targets HDAC3 to Inhibit p65 Deacetylation and Activate the NF-κB Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a subtype of stroke, and early brain injury (EBI) is a contributor to its unfavorable outcome. microRNA (miRNA) is abundantly expressed in the brain and participates in brain injury. This study investigated the effect of miR-452-3p on EBI after SAH. METHODS: The murine model of SAH was established. miR-452-3p expression was detected 48 h after the model establishment. Neurobehavioral function, blood-brain barrier permeability, brain water content, neuronal apoptosis, and inflammatory factors were evaluated. The cell model of SAH was induced by oxygen hemoglobin. Apoptosis rate, lactate dehydrogenase, and reactive oxygen species were detected. The targeting relationship between miR-452-3p and histone deacetylase 3 (HDAC3) was verified. The acetylation of p65 and the binding of HDAC3 to p65 were detected. The inhibitory protein of the nuclear factor κB pathway (IκBα) was detected. Suberoylanilide hydroxamic acid was injected into the SAH mice treated with miR-452-3p inhibitor. RESULTS: SAH mice showed upregulated miR-452-3p expression; reduced the neurological score; increased blood-brain barrier permeability, brain water content, and neuronal apoptosis; elevated pro-inflammatory factors; and reduced anti-inflammatory factors. SAH increased the apoptosis rate, lactate dehydrogenase release, and reactive oxygen species levels in oxygen-hemoglobin-treated neuron cells. Inhibition of miR-452-3p reversed the above trends. miR-452-3p targeted HDAC3. SAH upregulated p65 acetylation. miR-452-3p inhibitor promoted the binding of HDAC3 to p65, decreased p65 acetylation, and upregulated IκBα. Suberoylanilide hydroxamic acid reversed the protective effect of miR-452-3p inhibitor on SAH mice and aggravated brain injury. CONCLUSIONS: miR-452-3p targeted HDAC3 to inhibit the deacetylation of p65 and activate the nuclear factor κB pathway, thus aggravating EBI after SAH.

Genetic variants of CYP4F12 gene are associated with glioma susceptibility.

Glioma is a common and fatal primary malignant tumor of the central nervous system, and its prognosis is poor. To determine the susceptibility markers of gliomas in Chinese population we conducted a genome-wide association study (GWAS) of glioma in the Han Chinese population, with a total of 485 glioma cases and 485 controls. Genotyping was conducted using the Applied Biosystems Axiom Precision Medicine Diversity Array. Besides, we carried out imputation using IMPUTE 2.0 software, and the 1000 Genomes Phase 3 was used as the reference panel. The logistic regression model was used to analyze the association of each SNP with glioma risk, assuming an additive genetic model, which was implemented in PLINK version 1.9. Odds ratio (OR) and 95% confidence interval (CI) were estimated from logistic regression analysis with adjustment for age and gender. The results revealed that the SNP (rs688755) in the exon region of CYP4F12 at 19p13.12 reached genome-wide significance associated with gliomas (P = 2.35 × 10-8 , OR = 3.55, 95% CI = 2.20-5.74). Our findings provide deeper insight into the genetic contribution to glioma in different populations.

Long intergenic noncoding RNA 00021 promotes glioblastoma temozolomide resistance by epigenetically silencing p21 through Notch pathway.

Increasing findings are suggesting the vital roles of long noncoding RNAs (lncRNAs) in the glioblastoma tumorigenesis. However, whether the novel lncRNA LINC00021 modulates temozolomide (TMZ) resistance of glioblastoma is still unclear. Clinically, lncRNA LINC00021 was significantly up-regulated in glioblastoma, especially the TMZ-resistant tissue and cells, and the LINC00021 overexpression was closely correlated to TMZ resistance and unfavorable prognosis. Functionally, LINC00021 positively promoted the TMZ resistance and reduced apoptosis. Mechanistically, transcription factor E2F1 activated the expression of LINC00021. Moreover, LINC00021 regulated the glioblastoma TMZ resistance through Notch pathway and epigenetically silenced p21 expression via recruiting EZH2. Collectively, present research indicates the critical roles of lncRNA LINC00021 in glioblastoma genesis, providing a novel insight for TMZ resistance in glioblastoma.

Activation of BDNF-AS/ADAR/p53 Positive Feedback Loop Inhibits Glioblastoma Cell Proliferation.

Despite progress in conventional treatment for glioblastoma (GBM), the prognosis remains poor due to high tumor recurrence. Therefore, identification of new molecular mechanisms is a pressing need for betterment of GBM patient outcomes. qRT-PCR was used to determine BDNF-AS expression in GBM cells. CCK-8, EdU incorporation, and caspase-3 activity assays were employed to analyze biological functions of BDNF-AS. RIP and RNA pull-down were conducted to detect the interactions among BDNF-AS, ADAR, and p53. Actinomycin D was utilized to examine the stability of p53 mRNA. ChIP and luciferase reporter assays were performed to detect transcriptional activation of BDNF-AS by p53. We found that BDNF-AS was significantly downregulated in GBM cell lines, and its overexpression inhibited GBM cell growth, and promoted apoptosis. Importantly, we illustrated that BDNF-AS coupled with ADAR protein to potentiate stability of p53 mRNA and thus upregulate p53. Interestingly, we further identified p53 as a transcription factor of BDNF-AS, activating transcription of BNDF-AS. This study firstly demonstrated that BDNF-AS acted as a tumor suppressor in GBM and the positive feedback circuit of BDNF-AS/ADAR/p53 served an important mechanism to control GBM proliferation. Targeting this auto-regulatory loop may provide a potential therapeutic strategy for GBM patients.

Knockdown of SLC34A2 inhibits cell proliferation, metastasis, and elevates chemosensitivity in glioma.

Solute carrier 34 A2 (SLC34A2) is a member of SLC34 family that is a group of phosphate transporters. SLC34A2 has been reported to play critical roles in tumorigenesis and progression. However, the researches about the biological roles of SLC34A2 in glioma have not yet been reported. In this study, we analyzed the expression patterns of SLC34A2 in clinical glioma tumor tissues and cell lines. The results demonstrated that SLC34A2 was generally overexpressed in both glioma tissues and cell lines. To further investigate the roles of SLC34A2 in glioma, lentivirus containing specific SLC34A2 short hairpin RNA (sh-SLC34A2) was used to infect glioma cell lines U251 and U87 for the knockdown of SLC34A2. The following studies proved that SLC34A2 knockdown exhibited suppressive effects on cell proliferation and migration/invasion. SLC34A2 knockdown also inhibited epithelial-mesenchymal transition (EMT) phenotype, as evidenced by the increased E-cadherin expression, and the decreased N-cadherin and fibronectin expressions. Besides, knockdown of SLC34A2 enhanced the temozolomide (TMZ) sensitivity of U251 and U87 cells. In vivo tumorigenicity assay demonstrated that SLC34A2 knockdown inhibited tumor growth. Moreover, SLC34A2 knockdown suppressed the activation of epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in U87 cells. GW2974 (EGFR inhibitor) increased SLC34A2 knockdown-inhibited cell proliferation, migration/invasion, as well as enhanced SLC34A2 knockdown-increased the TMZ sensitivity of glioma cells. These findings suggested that SLC34A2 might be a new potential therapeutic target for the therapy of glioma patients.

Parallel triplex structure formed between stretched single-stranded DNA and homologous duplex DNA.

The interaction between the single-stranded DNA and the homologous duplex DNA is essential for DNA homologous repair. Here, we report that parallel triplex structure can form spontaneously between a mechanically extended ssDNA and a homologous dsDNA in protein-free condition. The triplex has a contour length close to that of a B-form DNA duplex and remains stable after force is released. The binding energy between the ssDNA and the homologous dsDNA in the triplex is estimated to be comparable to the basepairing energy in a B-form dsDNA. As ssDNA is in a similar extended conformation within recombinase-coated nucleoprotein filaments, we propose that the parallel triplex may form and serve as an intermediate during recombinase-catalyzed homologous joint formation.

Foliar antitranspirant and soil superabsorbent hydrogel affect photosynthetic gas exchange and water use efficiency of maize grown under low rainfall conditions.

BACKGROUND: Two lysimeter experiments with maize plants were conducted to investigate the effect of combined superabsorbent polymer (SAP) and fulvic acid (FA) application on photosynthetic gas exchange and water use efficiency (WUE) under deficit irrigation conditions. Soil SAP (45 kg hm-2 ) was applied while sowing, and FA solution (2 g L-1 ) was sprayed onto the crop canopy three times at later plant growth periods. RESULTS: Combining SAP and FA application significantly improved plant photosynthesis, chlorophyll contents and instantaneous WUE while maintaining optimal leaf stomatal transpiration. The effect of using the combined chemicals on photosynthesis and leaf instantaneous WUE was superior to the effects of their individual applications. Compared with plots not treated with chemicals, soil SAP significantly improved the yield by 12% and grain WUE by 10% when averaged across the two experiments, whereas foliar FA application did not affect yield and grain WUE. In contrast, the combined use of the two chemicals significantly increased the yield by 20% and grain WUE by 26%, largely attributed to the increase in grain number. CONCLUSION: Soil SAP and foliar FA use under low rainfall conditions had little influence on crop water consumption but improved plant WUE by enhancing photosynthesis and increasing kernel number. © 2018 Society of Chemical Industry.

GenomeLaser: fast and accurate haplotyping from pedigree genotypes.

UNLABELLED: We present a software tool called GenomeLaser that determines the haplotypes of each person from unphased high-throughput genotypes in family pedigrees. This method features high accuracy, chromosome-range phasing distance, linear computing, flexible pedigree types and flexible genetic marker types. AVAILABILITY AND IMPLEMENTATION: http://www.4dgenome.com/software/genomelaser.html.

Knockdown of STIM1 improves neuronal survival after traumatic neuronal injury through regulating mGluR1-dependent Ca(2+) signaling in mouse cortical neurons.

Activation of glutamate receptors and followed increase of intracellular calcium concentration is a key pathological mechanism involved in secondary neuronal injury after traumatic brain injury (TBI). Stromal interaction molecule (STIM) proteins are considered to be important players in regulating neuronal Ca(2+) homeostasis under normal aging and pathological conditions. Here, we investigated the role of STIM1 in regulating metabotropic glutamate receptor 1 (mGluR1)-related Ca(2+) signaling and neuronal survival by using an in vitro traumatic neuronal injury (TNI) model. The expression of STIM1 was significantly increased at both mRNA and protein levels after TNI. Down-regulation of STIM1 by specific small interfere RNA significantly preserved neuronal viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell death after traumatic injury. Moreover, knockdown of STIM1 significantly alleviated the mGluR1-related increase of cytoplasmic Ca(2+) levels after TNI. By analyzing Ca(2+) imaging in Ca(2+)-free conditions, we demonstrated that the mGluR1-dependent inositol trisphosphate receptor and/or ryanodine receptor-mediated Ca(2+) release from the endoplasmic reticulum after TNI is strongly attenuated in the absence of STIM1. Together, our results demonstrate that in the mammalian nervous system, STIM1 is a key regulator of mGluR1-dependent Ca(2+) signaling and knockdown of STIM1 might be an effective intervention target in TBI.

Increased 8-hydroxydeoxyguanosine in high-grade gliomas is associated with activation of autophagy.

AIM OF THE STUDY: To understand the interaction between oxidative stress and autophagy in gliomas of different grades. MATERIALS AND METHODS: In the present study, we analyzed levels of oxidative stress in 45 human glioma tumors, using the DNA oxidation marker 8-hydroxydeoxyguanosine (8-OHdG). In addition, we determined activation of autophagy in gliomas samples by assessing expression of microtubule-associated protein 1 light chain-3B (LC3B). To confirm our in vivo findings, in vitro studies using U87 cells were conducted. RESULTS: It was determined that the grade of gliomas, that is, different malignant degrees according to WHO classification, significantly affected level of 8-OHdG. High levels of 8-OHdG were present in high-grade gliomas. This trend was significant in male patients and in young adult patients (<50 years old). Further study showed increased expression of LC3B in high-grade gliomas. In addition, levels of 8-OHdG and expression of LC3B were positively correlated. Reducing autophagic activity by 3-methyladenine resulted in significantly increased intracellular reactive oxygen species (ROS) in U87 cells. CONCLUSIONS: Our study provides evidence that high levels of oxidative stress in high-grade gliomas are associated with autophagy activation that may play a protective role promoting the survival of high-grade gliomas under severe oxidative stress.

Predictive factors influencing outcome of early cranioplasty after decompressive craniectomy: a outcome prediction model study.

Objective: The timing of cranioplasty (CP) has become a widely debated topic in research, there is currently no unified standard. To this end, we established a outcome prediction model to explore the factors influencing the outcome of early CP. Our aim is to provide theoretical and practical basis for whether patients with skull defects after decompressive craniectomy (DC) are suitable for early CP. Methods: A total of 90 patients with early CP after DC from January 2020 to December 2021 were retrospectively collected as the training group, and another 52 patients with early CP after DC from January 2022 to March 2023 were collected as the validation group. The Nomogram was established to explore the predictive factors that affect the outcome of early CP by Least absolute shrinkage analysis and selection operator (LASSO) regression and Logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the prediction model. Calibration curve was used to evaluate the accuracy of data fitting, and decision curve analysis (DCA) diagram was used to evaluate the benefit of using the model. Results: Age, preoperative GCS, preoperative NIHSS, defect area, and interval time from DC to CP were the predictors of the risk prediction model of early CP in patients with skull defects. The area under ROC curve (AUC) of the training group was 0.924 (95%CI: 0.867-0.980), and the AUC of the validation group was 0.918 (95%CI, 0.842-0.993). Hosmer-Lemeshow fit test showed that the mean absolute error was small, and the fit degree was good. The probability threshold of decision risk curve was wide and had practical value. Conclusion: The prediction model that considers the age, preoperative GCS, preoperative NIHSS, defect area, and interval time from DC has good predictive ability.

Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma.

BACKGROUND: An anti-tumour activity has been demonstrated for α-solanine, a bioactive compound extracted from the traditional Chinese herb Solanum nigrum L. However, its efficacy in the treatment of gliomas and the underlying mechanisms remain unclear. The aim of this study was to investigate the inhibitory effects of α-solanine on glioma and elucidate its mechanisms and targets using network pharmacology, molecular docking, and molecular biology experiments. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to predict the potential targets of α-solanine. GeneCards was used to gather glioma-related targets, and the STRING online database was used to analyze protein-protein interaction (PPI) networks for the shared targets. Hub genes were identified from the resulting PPI network and further investigated using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, prognostic and gene set enrichment analyses (GSEA) were carried out to identify potential therapeutic targets and their underlying mechanisms of action in relation to the prognosis of gliomas. In vitro experiments were conducted to verify the findings from the network pharmacology analysis. RESULTS: A total of 289 α-solanine targets and 1149 glioma-related targets were screened, of which 78 were common targets. 11 hub genes were obtained, including SRC, HRAS, HSP90AA1, IGF1, MAPK1, MAPK14, KDR, STAT1, JAK2, MAP2K1, and IGF1R. The GO and KEGG pathway analyses unveiled that α-solanine was strongly associated with several signaling pathways, including positive regulation of MAP kinase activity and PI3K-Akt. Moreover, α-solanine (10 µM and 15 µM) inhibited the proliferation and migration but promoted the apoptosis of glioma cells. Finally, STAT1 was identified as a potential mediator of the effect of α-solanine on glioma prognosis. CONCLUSION: α-Solanine can inhibit the proliferation and migration of gliomas by regulating multiple targets and signalling pathways. These findings lay the foundation for the creation of innovative clinical anti-glioma agents.

Improving the mapping accuracy of soil heavy metals through an adaptive multi-fidelity interpolation method.

Soil heavy metal pollution poses a serious threat to environmental safety and human health. Accurately mapping the soil heavy metal distribution is a prerequisite for soil remediation and restoration at contaminated sites. To improve the accuracy of soil heavy metal mapping, this study proposed an error correction-based multi-fidelity technique to adaptively correct the biases of traditional interpolation methods. The inverse distance weighting (IDW) interpolation method was chosen and combined with the proposed technique to form the adaptive multi-fidelity interpolation framework (AMF-IDW). In AMF-IDW, sampled data were first divided into multiple data groups. Then one data group was used to build the low-fidelity interpolation model through IDW, while the other data groups were treated as high-fidelity data and used for adaptively correcting the low-fidelity model. The capability of AMF-IDW to map the soil heavy metal distribution was evaluated in both hypothetical and real-world scenarios. Results showed that AMF-IDW provided more accurate mapping results compared with IDW and the superiority of AMF-IDW became more evident as the number of adaptive corrections increased. Eventually, after using up all data groups, AMF-IDW improved the R2 values for mapping results of different heavy metals by 12.35-24.32%, and decreased the RMSE values by 30.35%-42.86%, indicating a much higher level of mapping accuracy relative to IDW. The proposed adaptive multi-fidelity technique can be equally combined with other interpolation methods and provide promising potential in improving the soil pollution mapping accuracy.

Development of a novel angiogenesis-related lncRNA signature to predict the prognosis and immunotherapy of glioblastoma multiforme.

Background: Long noncoding RNA (lncRNA) can regulate tumorigenesis, angiogenesis, proliferation, and other tumor biological behaviors, and is closely related to the growth and progression of glioma. The purpose of this research was to investigate the role of angiogenesis-related lncRNA in the prognosis and immunotherapy of glioblastoma multiforme (GBM). Methods: Differential analysis was carried out to acquire angiogenesis-related differentially expressed lncRNAs (AR-DElncRNAs). The AR-DElncRNAs were then subjected to univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses to construct a prognostic model. Based on the median risk score, patients were classified into high-risk and low-risk groups. Kaplan-Meier survival analysis was conducted to estimate the prognostic value of the prognostic model. In addition, a nomogram was built to predict individual survival probabilities by combining clinicopathological characteristics and a prognostic model. Furthermore, immune infiltration, immunotherapy, and drug sensitivity analyses were administered to investigate the differences between the high- and low-risk groups. Results: We identified 3 lncRNAs (DGCR5, PRKAG2-AS1, and ACAP2-IT1) that were significantly associated with the survival of GBM patients from the 255 AR-DElncRNAs based on univariate Cox and LASSO analyses. Then, a prognostic model was structured according to these 3 lncRNAs, from which we found that high-risk GBM patients had a worse prognosis than that of low-risk patients. Moreover, the risk score was determined to be an independent prognostic factor [hazard ratio (HR) =1.444; 95% confidence interval (CI): 1.014-2.057; P<0.05]. The immune microenvironment analysis revealed that the immune score, stromal score, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) score were significantly higher in the high-risk group than in the low-risk group. Neutrophils, macrophages, immature dendritic cells (iDCs), natural killer (NK) CD56dim cells, activated DCs (aDCs), and uncharacterized cells were different in the high- and low-risk groups. In addition, the high-risk group had a stronger sensitivity to immunotherapy. Furthermore, the sensitivity of 28 potential chemotherapeutic drugs differed significantly between the high- and low-risk groups. Conclusions: A novel angiogenesis-related lncRNA signature could be used to predict the prognosis and treatment of GBM.

3D multimodal image fusion based on MRI in the preoperative evaluation of microvascular decompression: A meta­analysis.

Neurovascular compression (NVC) is the main cause of hemifacial spasm (HFS) or trigeminal neuralgia (TN), and frequently occurs at the root entry zone of cranial nerves. Microvascular decompression (MVD) is an effective surgical treatment for TN and HFS caused by NVC. The accurate preoperative diagnosis of NVC is crucial to the evaluation of MVD as an appropriate treatment for TN and HFS. Three-dimensional (3D) time-of-flight magnetic resonance angiography (3D TOF MRA) and high resolution T2-weighted imaging (HR T2WI) are used to detect NVC prior to MVD; however, this combination alone has certain disadvantages. Multimodal image fusion (MIF) may combine two or more images from the same or different modalities, allowing neurosurgeons to use the reconstructed 3D model to observe anatomical details more clearly from different perspectives. The aim of the present meta-analysis was to evaluate the effect of 3D MIF based on 3D TOF MRA combined with HR T2WI in the preoperative diagnosis of NVC, and thus to evaluate its clinical application value in the preoperative evaluation of MVD. Relevant studies available on PubMed, Embase, Web of Science, Scopus, China National Knowledge Infrastructure and the Cochrane Library, and published from the inception of each database to September 2022, were retrieved. Studies using 3D MIF based on 3D TOF MRA combined with HR T2WI to diagnose NVC in patients with TN or HFS were included. The Quality Assessment of Diagnostic Accuracy Studies checklist was used to evaluate the quality of the included studies. The statistical software Stata 16.0 was used to perform the meta-analysis. Data extraction was performed by two independent investigators and discrepancies were resolved by discussion. Pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the receiver operating characteristic curve (AUROC) were calculated as the main summary effect size. The I² and Q-test were used to assess heterogeneity. The present search identified 702 articles, of which 7 (comprising 390 patients) fulfilled the inclusion criteria. Bivariate analysis indicated that the pooled sensitivity and specificity of 3D MIF based on 3D TOF MRA combined with HR T2WI for detecting NVC were 0.97 (95% CI, 0.95-0.99) and 0.89 (95% CI, 0.77-0.95), respectively. The pooled PLR was 8.8 (95% CI, 4.1-18.6), the pooled NLR was 0.03 (95% CI, 0.02-0.06) and the pooled DOR was 291 (95% CI, 99-853). The AUROC was 0.98 (95% CI, 0.97-0.99). The studies had no substantial heterogeneity (I2=0; Q=0.000; P=0.50). The present results suggested that 3D MIF based on 3D TOF MRA combined with HR T2WI had excellent sensitivity and specificity for diagnosing NVC in patients with TN or HFS. Therefore, this method should serve a key role in MVD preoperative evaluation.

Network pharmacology -based study on the mechanism of traditional Chinese medicine in the treatment of glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most common primary malignant brain tumors. Yi Qi Qu Yu Jie Du Fang (YYQQJDF) is a traditional Chinese medicine (TCM) prescription for GBM. The present study aimed to use a network pharmacology method to analyze the underlying mechanism of YQQYJDF in treating GBM. METHODS: GBM sample data, active ingredients and potential targets of YQQYJDF were obtained from databases. R language was used to screen differentially expressed genes (DEGs) between GBM tissues and normal tissues, and to perform enrichment analysis and weighted gene coexpression network analysis (WGCNA). The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to perform a protein‒protein interaction (PPI) analysis. A Venn diagram was used to obtain the core target genes of YQQYJDF for GBM treatment. Molecular docking was used to verify the binding between the active ingredient molecules and the proteins corresponding to the core target genes. Cell proliferation assays and invasion assays were used to verify the effect of active ingredients on the proliferation and invasion of glioma cells. RESULTS: A total of 73 potential targets of YQQYJDF in the treatment of GBM were obtained. Enrichment analyses showed that the biological processes and molecular functions involved in these target genes were related to the activation of the G protein-coupled receptor (GPCR) signaling pathway and the regulation of hypoxia. The neuroactive ligand‒receptor pathway, the cellular senescence pathway, the calcium signaling pathway, the cell cycle pathway and the p53 signaling pathway might play important roles. Combining the results of WGCNA and PPI analysis, five core target genes and their corresponding four core active ingredients were screened. Molecular docking indicated that the core active ingredient molecules and the proteins corresponding to the core target genes had strong binding affinities. Cell proliferation and invasion assays showed that the core active ingredients of YQQYJDF significantly inhibited the proliferation and invasion of glioma cells (P < 0.01). CONCLUSIONS: The present study predicted the possible active ingredients and targets of YQQYJDF in treating GBM, and analyzed its possible mechanism. These results may provide a basis and ideas for further research.

Targeting of MALT1 May Improve Functional Recovery and Attenuate Microglia M1 Polarization-Mediated Neuroinflammation During Spinal Cord Injury.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is involved in neural injury, neuroinflammation, microglia activation, and polarization, while its function in spinal cord injury (SCI) remains unclear. Thus, this study aimed to evaluate the role of MALT1 modification on SCI recovery and its underlying mechanism. SCI surgery or sham surgery was performed in Sprague-Dawley rats. Then, MALT1 knockdown or negative control lentivirus was injected into SCI rats. Subsequently, MALT1 expression, locomotor capability, neural injury, markers for microglia activation and polarization, inflammatory cytokine expressions, and nuclear factor (NF)-κB pathway were detected. SCI rats exhibited higher MALT1 expression, microglia activation and M1 polarization, neuroinflammation, and NF-κB pathway activation, while worse locomotor capacity compared to sham rats (all P < 0.05). In SCI rats, MALT1 knockdown alleviated Basso, Beattie, and Bresnahan score from 10 to 28 days and attenuated HE staining reflected neural injury (all P < 0.05). Besides, MALT1 knockdown declined the number of IBA1+ cells, IBA1+ iNOS+ cells, and IBA1+ CD86+ cells, while enhanced the number of IBA1+ Arg1+ cells and IBA1+ CD206+ cells in SCI rats (all P < 0.05). Meanwhile, MALT1 knockdown declined the expressions of IL-1ß, IL-6, and TNF-α in SCI (all P < 0.05), but did not affect IL-10 expression (P > 0.05). Furthermore, MALT1 knockdown suppressed NF-κB pathway activation validated by immunofluorescence staining and western blot assays (all P < 0.05). MALT1 knockdown improves functional recovery, attenuates microglia activation, M1 polarization, and neuroinflammation via inhibiting NF-κB pathway in SCI.