Association between thyroid hormone levels in the acute stage of stroke and risk of poststroke depression: A meta-analysis.

BACKGROUND: Thyroid hormones have been indicated to be associated with depression, but their relationship with poststroke depression (PSD) remains controversial. Therefore, we performed a meta-analysis to explore the correlation between thyroid hormone levels in acute stroke and PSD. METHODS: We searched databases for eligible studies. Standard mean differences (SMD) and 95% confidence intervals (CI) were applied to evaluate the association among levels of thyroid hormones, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), in acute stroke patients and the risk of PSD. RESULTS: A total of 13 studies were included in the analysis. Compared to non-PSD patients, PSD patients had remarkably lower serum TSH and FT3 levels (TSH: SMD = -0.59, 95%CI = -1.04 to -.15, p = .009; FT3: SMD = -0.40, 95%CI = -.51 to -.30, p = .000) and higher serum FT4 levels (SMD = 0.33, 95%CI = .07-.59, p = .013). Subgroup analysis showed that there may be a more statistically significant association between FT3 and the risk of PSD compared to TSH and FT4. CONCLUSIONS: Our results suggested that patients with lower serum TSH and FT3 levels as well as higher serum FT4 levels in the acute stage of stroke may be more susceptible to PSD.

Transcription factor YY1 mediates self-renewal of glioblastoma stem cells through regulation of the SENP1/METTL3/MYC axis.

Glioma is a primary brain tumor with limited treatment approaches and glioblastoma stem cells (GSCs) are manifested with the self-renewal capability and high tumorigenic capacity. This study was performed to investigate the regulatory effect of the SUMO-specific protease 1 (SENP1)/methyltransferase-like 3 (METTL3)/MYC axis on the self-renewal of GSCs mediated by transcription factor Yin Yang 1 (YY1). Following bioinformatics analysis and clinical and cellular experiments, we found that YY1 was highly expressed in GBM tissues and cells, while silencing its expression reduced the self-renewal ability of GSCs. Functionally, YY1 promoted the transcriptional expression of SENP1 by binding to the promoter region of SENP1, while the deSUMOase SENP1 facilitated the methylase activity of m6A through deSUMOylation of the methylase METTL3, thereby promoting the m6A modification of MYC mRNA via METL3 and promoting the expression of MYC. A nude mouse xenograft model of GBM was also constructed to examine the tumorigenicity of GSCs. The obtained findings demonstrated that YY1 promoted tumorigenicity of GSCs by promoting the expression of MYC in vivo. Conclusively, YY1 can transcriptionally upregulate the SUMOylase SENP1 and enhance the methylase activity of METTL3, resulting in the increased m6A modification level of MYC mRNA, thereby promoting the self-renewal of GSCs.

The therapeutic effect of an autologous and allogenic mixed glioma cell lysate vaccine in a rat model.

PURPOSE: Tumor immunotherapy has the advantages of high specificity, minimal damage to the patient's body, and a long-lasting anti-tumor effect. However, due to the existence of immune escape phenomenon, the effect of anti-tumor immunotherapy is still poor. Therefore, a cancer vaccine that reverses tumor-associated immunosuppression is a very promising approach for research and treatment. METHODS: Vaccines were prepared using autologous and allogeneic tumor cells and their lysates to syngeneic tumor cell lysates as immunogens. The glioma cell proliferation, apoptosis and the secretion level of MCP-2, IFN-γ were detected to evaluate the efficacy of this treatment against glioma in vitro. In addition, a rat glioma model was established to investigate the anti-tumor effect in vivo, and evaluated its efficacy by observing the changes of CD4 + T cells, CD8 + T cells, NK cells, and the level of IL-2 and IL-10 in peripheral blood before and after treatment. RESULTS: The C6 + 9L glioma cell lysate vaccine (C6 + 9L-CL) not only inhibited the proliferation of glioma cells and promoted their apoptosis in vitro, but also significantly inhibited the tumor growth in vivo and improved the survival time of rats. In addition, the C6 + 9L-CL vaccine enhanced the anti-tumor immune response by promoting the secretion of T cell chemokines MCP-2, IFN-γ and IL-2, and by stimulating the proliferation of T cells and NK cells in peripheral blood and glioma tissues. CONCLUSION: Our findings demonstrate the inhibitory effect of molecular mimic vaccines on glioma and provided a theoretical basis for molecular mimic hybrid vaccines as a potential therapeutic approach.

Case report: Overlapping syndrome mimicking infectious meningoencephalitis in a patient with coexistent MOG, NMDAR, mGluR5 antibody positivity.

A 38-year-old Chinese Han man presented with fever, headache and difficulty in language expression. The initial cerebrospinal fluid (CSF) analysis revealed lymphocytic-predominant pleocytosis with a normal glucose level, and magnetic resonance imaging (MRI) showed extensive cortical edema in left cerebral hemisphere. He received the antiviral treatment. However, one week later, he developed psychomotor agitation and seizures. Lumbar puncture was performed again and further testing for autoantibodies was conducted in both the CSF and serum. His CSF was positive for anti-myelin oligodendrocyte glycoprotein (MOG), anti-N-methyl-D-aspartate receptor (NMDAR) and anti-metabotropic glutamate receptor 5 (mGluR5) antibodies. He was diagnosed with overlapping syndrome of MOG antibody-related cerebral cortical encephalitis and anti-NMDAR, anti-mGluR5 autoimmune encephalitis. He received intravenous methylprednisolone and immunoglobulin, followed by oral prednisone and mycophenolate mofetil. His psychomotor agitation and seizures were relieved, and he gradually recovered his language expression ability. We reported for the first time a case that was positive for coexistent MOG, NMDAR, mGluR5 antibodies, which was initially misdiagnosed as infectious meningoencephalitis. This case widens the clinical spectrum of the overlapping syndrome recently reported.

Reduced PTCH2 expression is associated with glioma development through its regulation of the PTEN/AKT signaling pathway.

Mutations in the human protein patched homolog (PTCH) gene have been demonstrated to be associated with cancer development in several types of malignancy. However, the underlying mechanism of PTCH-associated cancer development remains poorly understood, to the best of our knowledge. In the present study, the expression of PTCH2 in glioma tumor tissues from The Cancer Genome Atlas (TCGA) database and clinical patients with glioma were measured. Reduced expression levels of PTCH2 were observed in patients with glioma with poor prognose. In vitro, overexpression of PTCH2 significantly suppressed the proliferation and invasion of the glioma cell lines, LN229 and U87-MG. Mechanistically, PTCH2 upregulated the expression of tumor suppressor PTEN, thereby leading to the suppression of pro-survival AKT signals in glioma. Reduced expression of PTEN and enhanced expression of AKT promoted glioma development in vitro and in vivo. Blockade of PTCH2/AKT signals efficiently strengthened the anticancer effects of chemotherapy and prolonged the survival time in tumor-bearing mice, which provided a novel insight into potential treatment strategies for glioma in the clinic.

TDO2 and tryptophan metabolites promote kynurenine/AhR signals to facilitate glioma progression and immunosuppression.

Tumor cells exhibit enhanced uptake and processing of nutrients to fulfill the demands of rapid growth of tumor tissues. Tryptophan metabolizing dioxygenases are frequently up-regulated in several tumor types, which has been recognized as a crucial determinant in accelerated tumor progression. In our study, we explored the specific role of tryptophan 2,3-dioxygenase 2 (TDO2) in glioma progression. Analysis of mRNA profiles in 325 glioma patients based on the rich set of CCGA database was performed, which revealed that high TDO2 expression was tightly correlated with poor prognosis in glioma patients. TDO2 increased intracellular levels of tryptophan metabolism in the kynurenine (Kyn) pathway in vitro and in vivo, resulting in sustained glioma cell proliferation. Mechanistically, overexpression of TDO2 promoted the secretion of Kyn, which in turn stimulated the activation of the aryl hydrocarbon receptor (AhR)/AKT signaling pathway, resulting in heightened proliferative properties and tumorigenic potential in glioma cells. Meanwhile, Kyn produced by tumor cells further suppressed the proliferation of functional T cells, thereby resulting in immunosuppression and enhanced tumor growth in glioma. Our study showed that TDO2-induced increase in tryptophan metabolite Kyn played a pivotal role in glioma development via the AhR/AKT pro-survival signals and immunosuppressive effects, suggesting that the use of TDO2 inhibitors in combination with chemotherapy may be a novel strategy to effectively and synergistically eliminate glioma cells.

Transcription factor SNAI2 exerts pro-tumorigenic effects on glioma stem cells via PHLPP2-mediated Akt pathway.

The current study aimed to investigate the effects associated with SNAI2 on the proliferation of glioma stem cells (GSCs) to elucidate its underlying molecular mechanism in the development of glioma. The expression of Snail family transcriptional repressor 2 (SNAI2) in glioma tissues was initially predicted via bioinformatics analysis and subsequently confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), which revealed that SNAI2 was highly expressed in glioma tissues as well as GSCs, with an inverse correlation with overall glioma patient survival detected. Loss- and gain- of-function assays were performed to determine the roles of SNAI2 and pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) on GSC viability, proliferation and apoptosis. Data were obtained indicating that SNAI2 promoted the proliferation of GSCs, while overexpressed PHLPP2 brought about a contrasting trend. As detected by chromatin immunoprecipitation, RT-qPCR and agarose gel electrophoresis, SNAI2 bound to the promoter region of PHLPP2 and repressed the transcription of PHLPP2 while SNAI2 was found to inhibit PHLPP2 resulting in activation of the Akt pathway. Finally, the roles of SNAI2 and PHLPP2 were verified in glioma growth in nude mice xenografted with tumor. Taken together, the key findings of the present study suggest that SNAI2 may promote the proliferation of GSCs through activation of the Akt pathway by downregulating PHLPP2.

HOXA-AS2 contributes to regulatory T cell proliferation and immune tolerance in glioma through the miR-302a/KDM2A/JAG1 axis.

Long non-coding RNAs (lncRNAs) have been manifested to manipulate diverse biological processes, including tumor-induced immune tolerance. Thus, we aimed in this study to identify the expression pattern of lncRNA homeobox A cluster antisense RNA 2 (HOXA-AS2) in glioma and decipher its role in immune tolerance and glioma progression. We found aberrant upregulation of lncRNA HOXA-AS2, lysine demethylase 2A (KDM2A), and jagged 1 (JAG1) and a downregulation of microRNA-302a (miR-302a) in glioma specimens. Next, RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter gene assay demonstrated that lncRNA HOXA-AS2 upregulated KDM2A expression by preventing miR-302a from binding to its 3'untranslated region. The functional experiments suggested that lncRNA HOXA-AS2 could promote regulatory T (Treg) cell proliferation and immune tolerance, which might be achieved through inhibition of miR-302a and activation of KDM2A/JAG1 axis. These findings were validated in a tumor xenograft mouse model. To conclude, lncRNA HOXA-AS2 facilitates KDM2A/JAG1 expression to promote Treg cell proliferation and immune tolerance in glioma by binding to miR-302a. These findings may aid in the development of novel antitumor targets.

Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a.

Glioma is regarded as an aggressive lethal primary brain tumor. Jumonji domain containing 1C (JMJD1C) is a H3K9 demethylase which participates in the progression of various tumors, but its specific function and underlying mechanism in glioma development remain undefined, which is the purpose of our work. We initially assessed JMJD1C expression in glioma tissues and cells using the assays of RT-qPCR and immunohistochemistry. Meanwhile, the H3K9 level at the microRNA (miR)-302a promoter region was measured by chromatin immunoprecipitation assay, while luciferase-based reporter assay was performed for validation of the binding affinity between miR-302a and methyltransferase-like 3 (METTL3). The effect of METTL3 on suppressor of cytokine signaling 2 (SOCS2) was subsequently analyzed by MeRIP-RT-qPCR. Finally, a xenograft tumor model was established in nude mice, followed by measurement of tumor-associated macrophages using flow cytometry. JMJD1C was poorly expressed in glioma tissues. Furthermore, JMJD1C increased miR-302a expression through promoting H3K9me1 demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. JMJD1C promoted M1 macrophage polarization and suppressed the growth of glioma xenografts through the miR-302a/METTL3/SOCS2 axis both in vivo and in vitro. In conclusion, JMJD1C could enhance M1 macrophage polarization to inhibit the onset of glioma, bringing a new insight into the contribution of JMJD1C to the pathobiology of glioma, with possible implications for targeted therapeutic method.

Effects of Sodium Valproate Monotherapy on Blood Liver Enzyme Levels in Patients with Epilepsy: A Meta-Analysis.

We conducted this meta-analysis to assess the effects of sodium valproate (VPA) monotherapy on blood liver enzymes in patients with epilepsy. PubMed, Web of Science, EBSCO, Cochrane Library, Wanfang, China national knowledge infrastructure databases were searched. Nine studies were included. Results showed: (1) The overall SMD for blood AST, ALT, and GGT levels of VPA monotherapy group versus control group were 0.70 (95% CI=0.31 to 1.09, Z=3.52, p=0.0004), 0.47 (95% CI=- 0.01 to 0.95, Z=1.91, p=0.06), 0.44 (95% CI=0.29 to 0.60, Z=5.55, p<0.00001), respectively. (2) In subgroup meta-analysis, increased blood AST and GGT levels were observed in epileptic minors (AST: total SMD=0.85, 95% CI=0.40 to 1.30, Z=3.69, p=0.0002; GGT: total SMD=0.46, 95% CI=0.29 to 0.63, Z=5.25, p<0.00001). Elevated blood ALT level was observed in Asian patients receiving VPA monotherapy (total SMD=0.70, 95% CI=0.51 to 0.90, Z=7.01, p<0.00001), and the early stage of VPA monotherapy (total SMD=0.93, 95% CI=0.57 to 1.29, Z=5.09, p<0.00001). Overall, our results indicated that blood AST and GGT were significantly increased in epileptic minors receiving VPA monotherapy. The elevation of blood ALT was observed in Asian patients and the early stage of VPA monotherapy. However, due to the small number of included studies, our results should be considered with caution.

Matrix stiffness promotes glioma cell stemness by activating BCL9L/Wnt/ß-catenin signaling.

Matrix stiffness is a key physical characteristic of the tumor microenvironment and correlates tightly with tumor progression. Here, we explored the association between matrix stiffness and glioma development. Using atomic force microscopy, we observed higher matrix stiffness in highly malignant glioma tissues than in low-grade/innocent tissues. In vitro and in vivo analyses revealed that culturing glioma cells on stiff polyacrylamide hydrogels enhanced their proliferation, tumorigenesis and CD133 expression. Greater matrix stiffness could obviously up-regulated the expression of BCL9L, thereby promoting the activation of Wnt/ß-catenin signaling and ultimately increasing the stemness of glioma cells. Inhibiting Wnt/ß-catenin signaling using gigantol consistently improved the anticancer effects of chemotherapy and radiotherapy in mice with subcutaneous glioma tumors. These findings demonstrate that a stiffer matrix increases the stemness of glioma cells by activating BCL9L/Wnt/ß-catenin signaling. Moreover, we have provided a potential strategy for clinical glioma treatment by demonstrating that gigantol can improve the effectiveness of traditional chemotherapy/radiotherapy by suppressing Wnt/ß-catenin signaling.

Regulation of Toll-like receptor-mediated inflammatory response by microRNA-152-3p-mediated demethylation of MyD88 in systemic lupus erythematosus.

OBJECTIVE: microRNAs (miRNAs) play critical roles in embryogenesis, cell differentiation and the pathogenesis of several human diseases, including systemic lupus erythematosus (SLE). Toll-like receptors (TLRs) are also known to exert crucial functions in the immune response activation occurring in the pathogenesis of autoimmune diseases like SLE. Herein, the current study aimed to explore the potential role of miR-152-3p in TLR-mediated inflammatory response in SLE. METHODS: We determined the miR-152-3p expression profiles in CD4+ T cells and peripheral blood mononuclear cells (PBMCs) harvested from patients with SLE and healthy controls, and analyzed the correlation between miR-152-3p expression and clinicopathological parameters. CD70 and CD40L expression patterns in CD4+ T cells were assessed by RT-qPCR and flow cytometry. ChIP was adopted to determine the enrichment of DNA methyltransferase 1 (DNMT1) in the promoter region of myeloid differentiation factor 88 (MyD88). RESULTS: The obtained findings revealed that miR-152-3p was highly-expressed in CD4+ T cells and PBMCs of patients with SLE, and this high expression was associated with facial erythema, joint pain, double-stranded DNA, and IgG antibody. DNMT1 could be enriched in the MyD88 promoter, and miR-152-3p inhibited the methylation of MyD88 by targeting DNMT1. We also found that silencing miR-152-3p inhibited MyD88 expression not only to repress the autoreactivity of CD4+ T cells and but also to restrain their cellular inflammation, which were also validated in vivo. CONCLUSION: Our study suggests that miR-152-3p promotes TLR-mediated inflammatory response in CD4+ T cells by regulating the DNMT1/MyD88 signaling pathway, which highlights novel anti-inflammatory target for SLE treatment.

Remodeling cancer stemness by collagen/fibronectin via the AKT and CDC42 signaling pathway crosstalk in glioma.

Cancer development is a complex set of proliferative progression, which arises in most cases via multistep pathways associated with various factors, including the tumor microenvironment and extracellular matrix. However, the underlying mechanisms of cancer development remain unclear and this study aimed to explore the role of extracellular matrix in glioma progression. Methods: The expression of type I collagen and fibronectin in tumor tissues from glioma patients was examined by immunofluorescence staining. The correlations between collagen/fibronectin and glioma progression were then analyzed. A 3D collagen/fibronectin cultured system was established for tumor cells culture in vitro. Quantitative, real-time PCR and western blot were used to detect PI3K/ATK and CDC42 signals associated proteins expression in glioma. We used in vitro Cell Counting Kit-8, colony formation, and tumorigenesis assays to investigate the function of PI3K/AKT and CDC42 signals associated proteins. A xenograft glioma mice model was also used to study the anticancer effects of integrin inhibitor in vivo. Results: Our study demonstrated that type I collagen and fibronectin collaborate to regulate glioma cell stemness and tumor growth. In a 3D collagen/fibronectin culture model, glioma cells acquired tumorigenic potential and revealed strengthened proliferative characteristics. More significantly, collagen/fibronectin could facilitate the activation of PI3K/AKT/SOX2 and CDC42/YAP-1/NUPR1/Nestin signaling pathways via integrin αvß3, eliciting sustained tumor growth and cancer relapse. Combination of the integrin signaling pathway inhibitor and the chemotherapeutic agent efficiently suppressed glioma cell proliferation and tumorigenic ability. Conclusion: We demonstrated that type I collagen and fibronectin could collaborate to promote glioma progression through PI3K/AKT/SOX2 and CDC42/YAP-1/NUPR1/Nestin signaling pathways. Blockade of the upstream molecular integrin αvß3 revealed improved outcome in glioma therapy, which provide new insights for eradicating tumors and reducing glioma cancer relapse.

A Hybrid Glioma Tumor Cell Lysate Immunotherapy Vaccine Demonstrates Good Clinical Efficacy in the Rat Model.

BACKGROUND: Conventional immunotherapy for glioma is not only expensive but also demonstrates less-than-desired clinical efficacy. In this study, we evaluated the immunotherapeutic efficacy of a tumor cell lysate-based hybrid glioma vaccine developed using a molecular-based approach. METHODS: First, the ability of the autologous (9L-cell lysate) and allogeneic (C6-cell lysate) vaccines against glioma, individually and in combination, to activate Fischer344 rat dendritic cells (DCs) was determined. Next, the activated DCs were co-cultured with T lymphocytes and screened for the optimal DC-to-T-cell ratio. The in vitro efficacy of the DC/T-cell vaccine formulations subjected to different immunogen treatments and co-cultured with glioma cells was evaluated based on glioma cell viability and monocyte chemoattractant protein (MCP)-2 and interferon (IFN)-γ secretion. Subsequently, the efficacy of the 9L + C6 hybrid vaccine was evaluated in 32 glioma rat models, randomly allocated to the following five treatment groups: blank control, tumor, vaccine treatment, thymosin treatment, and vaccine + thymosin treatment (combined treatment). Changes in survival duration, intracranial tumor volume, peripheral blood immune-cell (CD4+ T, CD8+ T, and natural killer [NK] cell) count, and serum cytokine (interleukin [IL]-2, IL-10) levels were assessed in these groups. RESULTS: The hybrid vaccine demonstrated the highest glioma cell apoptosis and the lowest cell viability and promoted MCP-2 and IFN-γ secretion in vitro. The vaccine treatment and combined treatment groups demonstrated longer survival duration, lower intracranial tumor volume, and higher immune cell glioma tissue infiltration and IL-2 secretion than the untreated tumor group, indicating the vaccine's good in vivo efficacy. Thymosin treatment had minimal effect in enhancing anti-glioma immunity. CONCLUSION: We demonstrated the feasibility of combining autologous and allogeneic tumor cell lysates to stimulate specific host cell immune response against glioma cells. The good clinical efficacy of our developed glioma hybrid vaccine in rat models suggests its potential clinical application.

The roles of ER stress in epilepsy: Molecular mechanisms and therapeutic implications.

Epilepsies are a diverse group of neurological disorders, which are characterized by spontaneous recurrent seizures. Although a wide range of pathogenic mechanisms such as alterations in ion channels, inflammation and neuronal loss have been reported to be implicated in the epileptogenesis, the underlying pathogenesis of epilepsy remains unclear currently. Endoplasmic reticulum (ER) stress is regarded as a condition that unfolded or misfolded proteins accumulate in the ER lumen. Excessive or prolonged ER stress causes the activation of the unfolded protein response (UPR) to buffer ER stress and restore ER homeostasis. Increasing evidence has indicated dysregulated ER stress during epileptogenesis, which may participate in various pathological processes associated with epilepsy. In this present review, we summarized recent advances in the involvement of ER stress in the pathogenesis of epilepsy. Additionally, the antiepileptic and neuroprotective effects of interventions targeting ER stress were also discussed.

A case report of primary central nervous system lymphoma.

Most patients with primary central system lymphoma (PCNSL) have immune dysfunction. PCNSL without immune dysfunction is rare and extremely challenging to diagnose. Here, we report the case of a 52-year-old woman without immune dysfunction who presented with PCNSL. The patient died a few months after diagnosis and during treatment. A review of this PCNSL patient's case highlighted that poor interpretation of imaging features and the poor correlation of laboratory test results with clinical findings led to a difficulty in making a diagnosis and administering the best treatment. For an accurate diagnosis of early stage PCNSL, positron-emission tomography computed tomography and corticosteroids should be used cautiously before stereotactic biopsy.

B7-H3 Regulates Glioma Growth and Cell Invasion Through a JAK2/STAT3/Slug-Dependent Signaling Pathway.

PURPOSE: The aim of this study was to explore the potential role of B7-H3 in malignant glioma progression and identify an innovative approach in clinical glioma therapy. METHODS: The protein expression of B7-H3 in high- and low-grade tumor tissues from glioma patients was assessed by immunohistochemistry. The proliferative and invasive ability of B7-H3-overexpressing or knockout glioma cells was analyzed in vitro and in vivo by CCK-8 assay and an orthotopic mouse glioma model, respectively. Activation of the JAK2/STAT3/Slug signaling pathway and epithelial-mesenchymal transition (EMT) was examined by Western blotting and immunofluorescence. The anticancer effects of napabucasin (NAP) and temozolomide (TMZ) were analyzed in an orthotopic mouse glioma model. RESULTS: The expression of B7-H3 was higher in high-grade than in low-grade tumor tissues from glioma patients. In line with this, overexpression of B7-H3 enhanced glioma cell proliferation, induced sustained glioma growth, and promoted glioma cell invasion in vitro and in vivo. Moreover, these effects were mediated through the activation of the JAK2/STAT3/Slug signaling pathway in B7-H3 overexpression glioma cells. We also found that B7-H3 induced EMT processes through downregulation of E-cadherin and upregulation of MMP-2/-9 expression, resulting in enhanced invasion of glioma cells. Finally, we show that the combination of NAP and TMZ significantly suppressed glioma growth and glioma cell invasion, both in vitro and in vivo. CONCLUSION: B7-H3 overexpression facilitated sustained glioma growth and promoted glioma cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway. Application of the STAT3 inhibitor NAP significantly suppressed glioma growth and invasion, and has potential as a therapeutic strategy for the treatment of glioma.

MicroRNA-30a suppresses self-renewal and tumorigenicity of glioma stem cells by blocking the NT5E-dependent Akt signaling pathway.

Over the past decade, increasing researches have demonstrated the implication of microRNAs (miRNAs or miRs) in tumorigenicity of glioma stem cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. Herein, we aim to investigate the role of miR-30a in the proliferation and self-renewal of GSCs and the possible mechanism in relation to ecto-5'-nucleotidase (NT5E)-dependent Akt signaling pathway. RT-qPCR and Western blot analysis were performed to determine the expression of miR-30a and NT5E in glioma tissues and cell lines. GSCs were isolated from glioma cells and identified using flow cytometry. The relationship between miR-30a and NT5E was determined by dual-luciferase reporter gene assay. Gain- and loss-of-function experiments were performed to examine the effects of miR-30a and NT5E on sphere formation, colony formation, and proliferation of GSCs in vitro, as well as orthotopic tumor growth of GSCs in nude mice. Additionally, the Akt signaling pathway was blocked with an Akt inhibitor, LY294002, to investigate its involvement in the regulatory effect of miR30a. miR-30a was poorly expressed in glioma tissues and cell lines as well as GSCs. NT5E, highly expressed in GSCs, was identified as a target of miR-30a. In addition, miR-30a upregulation or NT5E silencing could reduce GSC sphere formation, clone formation, proliferation, and orthotopic tumor growth in nude mice. Moreover, miR-30a inhibited the activation of the Akt signaling pathway by targeting NT5E, and ultimately suppressing the self-renewal and orthotopic tumor growth of GSCs. Our results demonstrate that miR-30a targets NT5E to inhibit the Akt signaling pathway, by which could suppress the self-renewal and orthotopic tumor growth of GSCs. Those findings may provide theoretical basis of miR-30a as a therapeutic target to suppress the glioma progression.

Botulinum toxin A treatment for post-herpetic neuralgia: A systematic review and meta-analysis.

The present meta-analysis study aimed to investigate the safety and efficacy of local administration of botulinum toxin (BTX-A) vs. lidocaine in the treatment of post-herpetic neuralgia. A systematic search of the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, Chongqing VIP Information Co. and Chinese Biomedical Literature Database was performed to identify randomized controlled trials (RCTs) comparing BTX-A and lidocaine in the treatment of post-herpetic neuralgia. The primary outcomes were Visual Analogue Scale (VAS) pain scores at 1, 2 and 3 months after treatment and the effective rate. Secondary outcomes were scores on the McGill pain questionnaire and adverse event rate. A total of 7 RCTs comprising 752 patients were included. The VAS pain score was significantly lower at 1 month [mean difference (MD)=-2.31; 95% CI: -3.06, -1.56; P<0.00001)], 2 months (MD=-2.18; 95% CI: -2.24, -2.11; P<0.00001) and 3 months (MD=-1.93; 95% CI: -3.05, -0.82; P=0.0007) after treatment, the effective rate was significantly higher (odds ratio=2.9; 95% CI: 1.71, 4.13; P<0.0001) and scores on the McGill pain questionnaire were significantly lower (MD=-10.93; 95% CI: -21.02, -0.83; Z=2.12; P=0.03) in patients who received BTX-A for post-herpetic neuralgia compared to those who received lidocaine. There was no difference in the adverse event rate between treatments. In conclusion, BTX-A has potential as a safe and effective treatment option for post-herpetic neuralgia. Further large and well-designed RCTs are required to confirm this conclusion.

Regulatory roles of the miR-200 family in neurodegenerative diseases.

Neurodegenerative diseases are chronic and progressive disorders which are not effectively treated through adopting conventional therapies. For this unmet medical need, alternative therapeutic methods including gene-based therapies are emphasized. MicroRNAs (miRNAs) are small non-coding RNAs which can regulate gene expression at the post-transcriptional level. In recent years, dysregulated miRNAs have been indicated to be implicated in the occurrence and development of neurodegenerative diseases. They are investigated as candidates for diagnostic and prognostic biomarkers, as well as therapeutic targets. The miR-200 family consists of miR-200a, -200b, -200c, -141, and -429. Numerous studies have found that miR-200 family members are associated with the pathogenesis of neurodegenerative diseases. It is reported that miR-200 family members are aberrantly expressed in several neurodegenerative diseases, participating in various cellular processes including beta-amyloid (Aß) secretion, alpha-synuclein aggregation and DNA repair, etc. In the present review, we summarize the recent progress in the roles of miR-200 family in neurodegenerative diseases.