Prognostic Potential of METTL7B in Glioma

<b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> The expression of METTL7B in glioma and adjacent normal tissues were examined by using TCGA, Chinese Glioma Genome Atlas (CGGA) database, and clinical tissues. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Neuroprotective Effect of HOTAIR Silencing on Isoflurane-Induced Cognitive Dysfunction via Sponging microRNA-129-5p and Inhibiting Neuroinflammation

<b><i>Introduction:</i></b> This article purposed to detect the function of the HOTAIR and HOTAIR/microRNA-129-5p (miR-129-5p) axis on the isoflurane (ISO)-injured cells and rat, and propounded a novel perspective in exploring the molecular pathogenesis of ISO damage. <b><i>Methods:</i></b> The expression of HOTAIR and miR-129-5p was tested by quantitative real-time PCR. The viable cells were identified using MMT, and the apoptotic cells were provided by flow cytometry. The concentration of proinflammatory indicators was revealed by enzyme-linked immunosorbent assay kits. The function of HOTAIR on oxidative stress was detected by commercial kits. A luciferase assay was performed to confirm the relationship between miR-129-5p and HOTAIR. The Morris water maze test was conducted to elucidate the cognition of SD rats. <b><i>Results:</i></b> The expression of HOTAIR was enhanced and the expression of miR-129-5p was lessened in the ISO-evoked SD rats and HT22 cells. The interference of HOTAIR reversed the injury of ISO on cell viability, apoptosis, inflammation, and oxidative stress. Besides, HOTAIR might be a target ceRNA of miR-129-5p. MiR-129-5p abrogated the function of silenced HOTAIR on cell viability, cell apoptosis, inflammation, and oxidative stress. Moreover, in vivo, the intervention of HOTAIR reversed the influence of ISO on cognition and oxidative stress by binding miR-129-5p. <b><i>Discussion/Conclusion:</i></b> Lowly expressed HOTAIR contributed to the recovery of the ISO-injured HT22 cell model from the abnormal viability, apoptosis, inflammation, and oxidative stress by regulating miR-129-5p. miR-129-5p mediated the function of HOTAIR on cognition and oxidative balance in the ISO-managed SD rat model.

Berberine Protects against Neurological Impairments and Blood-Brain Barrier Injury in Mouse Model of Intracerebral Hemorrhage

<b><i>Background:</i></b> Elevation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signaling can suppress intracerebral hemorrhage (ICH)-induced neurological impairments. As an isoquinoline alkaloid, Berberine exerts neuroprotective effects in neurological disease models with activated AMPK/PGC1α signaling. <b><i>Aim:</i></b> We aim to study the effect of Berberine on ICH-induced brain injury and explore the potential molecular mechanism. <b><i>Methods:</i></b> ICH model was established in mice through intracerebral injection of autologous whole blood, followed by treatment with Berberine. Neurological impairments were assessed by the modified neurological severity score and behavioral assays. Brain edema and blood-brain barrier (BBB) integrity were assessed by water content in the brain, amount of extravasated Evans blue, and BBB tight junction components. Neuroinflammatory responses were assessed by inflammatory cytokine levels. AMPK/PGC1α signaling was examined by AMPK mRNA expression and phosphorylated AMPK and PGC1α protein levels. <b><i>Results:</i></b> Berberine (200 mg/kg) attenuated ICH-induced neurological deficits, motor and cognitive impairment, and BBB disruption. Berberine also suppressed ICH-induced inflammatory responses indicated by reduced production of inflammatory cytokines. Finally, Berberine drastically elevated AMPK/PGC1α signaling in the hemisphere of ICH mice. <b><i>Conclusion:</i></b> Our findings suggest that Berberine plays an important neuroprotective role against ICH-induced neurological impairments and BBB injury, probably by inhibition of inflammation and activation of AMPK/PGC1α signaling.

Expression of Zinc-Finger Antiviral Protein in hCMEC/D3 Human Cerebral Microvascular Endothelial Cells: Effect of a Toll-Like Receptor 3 Agonist

<b><i>Introduction:</i></b> Invasion of viruses into the brain causes viral encephalitis, which can be fatal and causes permanent brain damage. The blood-brain barrier (BBB) protects the brain by excluding harmful substances and microbes. Brain microvascular endothelial cells are important components of the BBB; however, the mechanisms of antiviral reactions in these cells have not been fully elucidated. Zinc-finger antiviral protein (ZAP) is a molecule that restricts the infection of various viruses, and there are 2 major isoforms: ZAPL and ZAPS. Toll-like receptor 3 (TLR3), a pattern-recognition receptor against viral double-stranded RNA, is implicated in antiviral innate immune reactions. The aim of this study was to investigate the expression of ZAP in cultured hCMEC/D3 human brain microvascular endothelial cells treated with an authentic TLR3 agonist polyinosinic-polycytidylic acid (poly IC). <b><i>Methods:</i></b> hCMEC/D3 cells were cultured and treated with poly IC. Expression of ZAPL and ZAPS mRNA was investigated using quantitative reverse transcription-polymerase chain reaction, and protein expression of these molecules was examined using western blotting. The role of nuclear factor-κB (NF-κB) was examined using the NF-κB inhibitor, SN50. The roles of interferon (IFN)-β, IFN regulatory factor 3 (IRF3), tripartite motif protein 25 (TRIM25), and retinoic acid-inducible gene-I (RIG-I) in poly IC-induced ZAPS expression were examined using RNA interference. Propagation of Japanese encephalitis virus (JEV) was examined using a focus-forming assay. <b><i>Results:</i></b> ZAPS mRNA and protein expression was upregulated by poly IC, whereas the change of ZAPL mRNA and protein levels was minimal. Knockdown of IRF3 or TRIM25 decreased the poly IC-induced upregulation of ZAPS, whereas knockdown of IFN-β or RIG-I did not affect ZAPS upregulation. SN50 did not affect ZAPS expression. Knockdown of ZAP enhanced JEV propagation. <b><i>Conclusion:</i></b> ZAPL and ZAPS were expressed in hCMEC/D3 cells, and ZAPS expression was upregulated by poly IC. IRF3 and TRIM25 are involved in poly IC-induced upregulation of ZAPS. ZAP may contribute to antiviral reactions in brain microvascular endothelial cells and protect the brain from invading viruses such as JEV.

Lymphocyte Subsets Are Associated with Disease Status in Neuromyelitis Optica Spectrum Disorders

<b><i>Objective:</i></b> At present, studies on lymphocytes are mostly conducted on CD19⁺ B cells and CD27⁺ B cells in neuromyelitis optica spectrum disorders (NMOSDs), but the exact changes in lymphocyte subsets (CD19⁺ B cells, CD3⁺ T cells, CD4⁺ Th cells, CD8⁺ Ts cells, the CD4⁺/CD8⁺ ratio, and NK [CD56+ CD16] cells) have rarely been studied. This study aimed to assess lymphocyte subset changes in patients with NMOSD. <b><i>Methods:</i></b> We performed a cross-sectional study of consecutive patients with acute NMOSD (<i>n</i> = 41), chronic NMOSD (<i>n</i> = 21), and healthy individuals (<i>n</i> = 44). Peripheral blood samples were obtained upon admission, and lymphocyte subsets were analyzed by flow cytometry. Levels of lymphocyte subsets among 3 groups were compared and its correlation with the length of spinal cord lesions was analyzed. <b><i>Results:</i></b> The levels of peripheral blood CD19⁺ B cells were significantly higher in patients with acute and chronic NMOSD than in healthy controls (HCs) (17.91 ± 8.7%, 13.08 ± 7.562%, and 12.48 ± 3.575%, respectively; <i>p</i> &#x3c; 0.001) and were positively correlated with the length of spinal cord lesions in acute NMOSD (<i>r</i> = 0.433, <i>p</i> &#x3c; 0.05). The peripheral blood CD4⁺/CD8⁺ ratio was significantly lower in patients with acute NMOSD and chronic NMOSD than in HCs (1.497 ± 0.6387, 1.33 ± 0.5574, and 1.753 ± 0.659, respectively; <i>p</i> &#x3c; 0.05), and the levels of peripheral blood NK (CD56+ CD16) cells were significantly lower in patients with acute and chronic NMOSD than in HCs (13.6 ± 10.13, 11.11 ± 7.057, and 14.7 [interquartile range = 9.28], respectively; <i>p</i> &#x3c; 0.01). <b><i>Conclusions:</i></b> The levels of certain subsets of peripheral blood lymphocytes are associated with disease status in NMOSD.

The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

<b><i>Introduction:</i></b> Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. <b><i>Methods:</i></b> The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including inter­leukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. <b><i>Results:</i></b> The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. <b><i>Conclusion:</i></b> Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

Effects of Long Noncoding RNA H19 on Isoflurane-Induced Cognitive Dysregulation by Promoting Neuroinflammation

<b><i>Introduction:</i></b> Isoflurane (ISO) may cause neuronal apoptosis and synaptic disorder during development, and damage long-term learning and memory function. This observation aimed to study the function of H19 in vitro and in vivo tests and the further mechanism was identified. <b><i>Methods:</i></b> ISO cell models and rat models were established and reactive oxygen species (ROS) identified. The viability and apoptosis of HT22 cells were detected by the MTT and flow cytometer. Morris water maze test was conducted to analyze the neurotoxicity of ISO on spatial learning and memory ability. Quantitative PCR was the method to verify the expression of H19. The concentration of inflammatory indicators was identified by enzyme-linked immunosorbent assay. <b><i>Results:</i></b> 1.5% and 2% ISO led to the neurotoxicity of HT22 cells and increased expression of H19. Silenced H19 meliorated these adverse impacts of ISO. Interference of H19 exerted neuroprotective roles by repressing modified neurological severity score, inhibiting escape latency, elevating distance and time of target area, and controlling ROS and inflammation. MiR-17-5p might be a promising competing endogenous RNA of H19. The expression of miR-17-5p was reduced in the ISO group and reversed by the absence of H19. <b><i>Conclusion:</i></b> Our results of in vitro and in vivo assay indicated that the absence of HT22 is a neuroprotective regulator of cognition and inflammation by accumulating miR-17-5p.

Clinical Heterogeneity in Acute Symptomatic Seizures due to Autoimmune Encephalitis Related to GAD65 Antibodies

<b><i>Introduction:</i></b> This study aimed to explore the diversity and clinical features of acute symptomatic seizures due to autoimmune encephalitis related to anti-glutamate decarboxylase (GAD) 65 antibodies. <b><i>Methods:</i></b> Clinical data of a series of 6 patients positive for anti-GAD65 antibodies were retrospectively analyzed. <b><i>Results:</i></b> Five of the patients were male and 1 was a female, with a median age of 44.1 years (range 18–70 years). Seizure forms were varied in 6 patients when they were admitted to the hospital: 3 cases of seizures only and 3 accompanied by other symptoms, such as mental disorder, cognitive impairment, cerebellar ataxia, and ocular movement disorder. Three patients (50%) had coexisting systemic autoimmune diseases, including diabetes mellitus, vitiligo, and hyperthyroidism. Five patients (83%) had abnormal brain MRI findings. They were all treated by immunotherapy, 5 of 6 patients improved significantly but relapsed after withdrawing methylprednisolone, and 1 patient got deteriorated. None of them were diagnosed with tumors. <b><i>Conclusions:</i></b> Clinical features of acute symptomatic seizures related to GAD65 antibodies are diverse, and early and continuous immunotherapy is necessary for patients.

The Effect of Interferon-Beta Therapy on T-Helper 17/miR-326 and T-Helper 1/miR-29b-3p Axis in Relapsing-Remitting Multiple Sclerosis Patients

<b><i>Background:</i></b> We aimed to evaluate the therapeutic effects of interferon-beta (IFN-β) on hsa-miR29b-3p and hsa-miR326 in isolated T-helper (Th)1 and Th17 cells expressed by relapsing-remitting multiple sclerosis (RRMS) patients before and after 1 year of treatment with IFN-β. <b><i>Methods:</i></b> The study was done on 19 RRMS patients pre- and posttreatment with IFN-β to evaluate the frequency of Th1 and Th17 cells by flow cytometry. The expression level of hsa-miR-29b-3p and hsa-miR-326 in isolated Th1 and Th17 cells was assessed by quantitative polymerase chain reaction. Enzyme-linked immunosorbent assay was also used to measure the plasma levels of I interferon -gamma and interleukin (IL)-17A. <b><i>Results:</i></b> Th17 cells and plasma levels of IL-17A decreased in RRMS patients after IFN-β therapy but hsa-miR-29b-3p and hsa-miR-326 expression had no significant change in treated RRMS patients versus baseline. <i>MxA</i> gene expression was significantly induced upon IFN-β therapy in patients with RRMS. <b><i>Conclusion:</i></b> IFN-β therapy is more effective on Th17 than Th1, but it does not reform altered expression of hsa-miR-326 and hsa-miR-29b-3p in Th17 and Th1, respectively.