Gliomas are the highly aggressive brain tumor and also the most devastating human tumors. The latent TGF binding proteins (LTBP) had been found to be involved in malignant biological process and could be used as potent biomarkers in several solid tumors. While the role of LTBP family in human glioma remain to be elucidated.
Glioma is a malignant brain cancer that exhibits high invasive ability and poor prognosis. MicroRNA (miR)‑181d has been reported to be involved in the development of glioma. Therefore, the aim of the present study was to investigate whether miR‑181d affected cellular progression by influencing the insulin like growth factor (IGF1)/PI3K/AKT axis. Western blot analysis was performed to analyze the expression levels of specific proteins, and a Cell Counting Kit‑8 assay was used to assess the proliferative ability of cells. Cell cycle progression and cellular apoptosis were both measured using flow cytometry. The results indicated that miR‑181d promoted cellular proliferation and cell cycle progression, while suppressing cellular apoptosis via the IGF1/PI3K/AKT axis. It was demonstrated that the IGF1 and PI3K/AKT inhibitors reversed these observed functions of miR‑181d. Furthermore, miR‑181d enhanced the growth of glioma xenografts in vivo, promoted cell cycle progression and suppressed cellular apoptosis within glioma xenograft tissues. Therefore, this newly identified miR‑181d/IGF1/PI3K/AKT axis may provide novel insights into the pathogenesis of glioma.
Abstract Background Gliomas are the most common malignant tumors of the central nervous system in adults, glioblastoma is notorious for its highly metastatic and recurrent, accounting for approximately 50% of all gliomas. Exploring its molecular mechanism is urgently needed for the treatment and prognosis evaluation of gliomas. Transmembrane BAX inhibitor motif-containing 1 (TMBIM1) has been reported to be associated with non-alcoholic steatohepatitis, tumor and other diseases. However, the role of TMBIM1 in GBM and the underlying mechanisms remains unclear. Methods The expression level and prognostic value of TMBIM1 in gliomas were investigated by public datasets, and further confirmed by western blot and immunohistochemistry (IHC) in our tissues. Intracranial xenograft model, IHC and western blot were used to evaluate the functional role of TMBIM1. Results TMBIM1 was over-expressed in GBM, and its high expression reduced the survival time of glioma patients. TMBIM1 induced EMT and autophagy, and inhibition of autophagy reverses TMBIM1-regulated EMT in vitro and in vivo. Intracranial xenograft model showed the survival time of mice in TMBIM1 knockdown group treated with chloroquine (CQ)was significantly prolonged. The loss of E-cadherin expression is considered the foundation of EMT, and we subsequently demonstrated that TMBIM1 stimulating autophagic degradation of E-cadherin via AMPK/mTOR/ULK1 axis. Conclusion Our study provides a novel mechanism for the regulation of EMT in the process of gliomas metastasis, indicating that inhibition of TMBIM1 activity to attenuate autophagy may be a potential strategy for the treatment of gliomas.
Traditionally, cerebral arteriovenous malformations (cAVMs) are surgically treated with microscopy, and no cases receive full neuroendoscopy. We operated on two small cAVMs with hematoma under a neuroendoscope, and the two patients obtained excellent results.To explore the feasibility of treating cAVMs with a full transcranial neuroendoscopic approach.The clinical data and operative techniques were collected and described for two patients who were diagnosed with cAVMs with hematoma and treated via a full transcranial neuroendoscopic approach.In the two patients, the hematomas were successfully evacuated, and the AVMs were removed simultaneously; both patients had achieved excellent recoveries at discharge.To our knowledge, this is the first report in the literature to successfully treat cAVMs with hematoma with a full transcranial neuroendoscopic approach, showing that this approach is feasible and may be an alternative for small ruptured cAVMs. However, while the feasibility of attempting this approach was demonstrated, it was difficult to certify its obvious advantage. Nevertheless, we believe that this approach might be difficult for middle and large AVMs due to the shortcomings of neuroendoscopy. More cases and practice are needed to confirm the merits and limitations of this new approach for AVMs.
OBJECTIVE To explore the clinical effects of posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kummell disease with kyphosis. METHODS Twenty-four patients with Kummell disease complicated with kyphosis treated by posterior short-segment pedicle screw internal fixation combined with vertebroplasty from January 2016 to December 2018 were retrospectively analyzed, including 6 males and 18 females, aged 63 to 85 (73.1±6.5) years old. The clinical effect was evaluate by visual analogue scale (VAS), Oswestry Disability Index (ODI), the anterior height of injured vertebral body, and the sagittal Cobb angle of the affected segment beforeoperation, at 3 days and final follow up after operation. And the surgical complications were observed. RESULTS All 24 patients were followed up from 12 to 24 months with an average of (15.5±3.2) months. The VAS score was decreased from 5.21±1.06 preoperatively to 2.38±0.58 at 3 days postoperatively and 1.71±0.75 at final follow-up;ODI was decreased from (50.4±13.5)% preoperatively to (20.9±8.0)% at 3 days postoperatively and (16.7±9.6)% at final follow-up;the anterior height of injured vertebral body was restored from (8.0±4.2) mm before surgery to (18.1±5.0) mm at 3 days after surgery and (16.8±5.1) mm at final follow up;the sagittal Cobb angle of affected segment was decreased from (19.5±6.3)° preoperatively to (7.6±2.1)° at 3 days after surgery and(8.4±1.7)° at final follow-up. VAS, ODI, anterior height of injured vertebral body, and sagittal Cobb angle of affected segment were significantly improved at 3 days after operation and at final follow-up (P<0.05). Two patients had complications, including asymptomaticcement leakage in 1 patient and superficial wound infection in 1 patient. CONCLUSION Posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kummell disease with kyphosis has relatively small surgical trauma, excellent clinical results, good vertebral height recovery, satisfactory correction of kyphotic angle, and fewer complications, etc. It is a safe and effective surgical method to treat Kummell disease with kyphosis.
Abstract Background: Glioma is the most common primary brain tumor and represents one of the most aggressive and lethal types of human cancer. BCL7 family has been found in several cancer types and could be involved in tumor progression. While the role of BCL7 family in human glioma has remained to be elucidated. Methods: Paraffin-embedded tumor samples were obtained to detect BCL7 expression by performing in glioma. Data (including normalized gene expression and corresponding clinical data) were obtained from Gliovis, CGGA, GEO, cBioportal and Oncomine and were used to investigate BCL7 genes expression in glioma. Survival analyses were calculated by Kaplan-Meier methods and Cox regression analysis in TCGA and CGGA. Gene Set Enrichment Analyses (GSEA) and gene ontology (GO) analysis was employed to perform the biological processes enrichment. Results: BCL7A expression in glioma tissues was lower compared to non-tumor brain tissues (NBT), and exhibited a negative correlation with glioma grades. Results from Immunohistochemical (IHC) staining and public dataset validation demonstrated that BCL7B and BCL7C were highly expressed in glioma tissues compared to NBT. Cox regression analysis identified BCL7A as the only gene in the BCL7 family that was independently associated with the prognosis of lower-grade glioma (LGG) and glioblastoma (GBM). GO and GSEA analyses revealed the potential contribution of BCL7A in adaptive immune response and neutrophil activation in the tumor microenvironment. Moreover, we found taht BCL7A had no prognostic effect on the overall survival of GBM patients who received IR only; however, patients who received chemotherapy (TMZ) combined with IR in the high BCL7A group survived longer than patients in the low BCL7A group (HR=0.346, P<0.05). Conclusion: BCL7A is a new tumor suppressor gene and can be adopted as a biomarker for independent prognosis in glioma and to evaluate response to TMZ.
Background: Ventilator-associated pneumonia (VAP) is one of the major public health problems, most commonly caused by Acinetobacter baumannii (Ab). In this study, by investigating the BALF exosome microRNA and serum metabolomic profiles, we aim to study the association between lung tissue derived exosome microRNAs and global metabolism alteration among patients with VAP caused by Ab infection.Methods: Consecutive patients admitted for pulmonary infection were enrolled. Demographic and biochemical measurements were collected and serum samples were obtained after overnight fasting upon admission. Bronchoscopy was performed and bronchial lavage was collected for patients with pulmonary infection. Exosome was extracted using SBI kit and microRNA was sequenced afterwards. Nontargeted metabolomics was applied to demonstrate metabolic profiles.Results: We have found significant alteration of microRNA profile in BALF exosomes in the patients with VAP caused by Ab infection; Gene Ontology analysis further identified its function in systemic metabolism. The expression pattern of differential exosome microRNAs in the lung, liver and circulation implied that BALF exosomes from both immune and structural cells in the lung might carry microRNAs into the circulation to target systemic metabolism alteration. The serum metabolomic profile and ratio of biological significance were meanwhile differentially regulated, correlating to differential expression of microRNAs in VAP patients with Ab infection.Conclusions: Our data summarized the dysregulated serum metabolism and exosome microRNA excretion in VAP patients with Ab infection. The correlation between BALF exosome microRNA in cellular metabolic pathway and dysregulated metabolites highlight potential biomarkers and therapeutics for diagnosing and treating Ab infection.Funding Statement: This study was supported by National Natural Science Foundation of China (81500016，81800390), the Natural Science Foundation of Shaanxi province (2017JM8016, 2018KW067, 2016SF217), the Fundamental Research Funds for the Central Universities in China(1191329724, 191329849)， and the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China ((No.XJTU1AF-CRF-2018-025).Declaration of Interests: The authors state: "None declared."Ethics Approval Statement: Written informed consent was obtained according to the Declaration of Helsinki, and was approved by the ethics committee (IRB committee: Xi’an Jiaotong University, project approval number 2018(6-169)).
Objective To investigate the effect of over-expression of ROBO4 on permeability of human renal glomerular endothelial cells (HRGECs) in high glucose medium. Methods HRGECs infected with recombinant lentiviral vector ROBO4 were cultured in high glucose or low glucose medium in vitro. The protein levels of ROBO4 and ARF6 in each group were detected by Western blotting. The endothelial permeability was measured by the efflux of fluorescein isothiocyanate-dextran (FITC-Dextran) permeated through the monolayer endothelial cells using Transwell cell model system. The cell viability after lentivirus transfection was measured by CCK8 assay. Results The transfection rate of lentiviruses in HRGECs reached 80% 72h after, and obvious over-expression of ROBO4 protein was in transformed cells compared with the empty vector group (P<0.05). The lentivirus-mediated ROBO4 transfection did not affect cell viability of HRGECs. Compared with the low glucose group, the expression of ROBO4 increased obviously after 12h, but declined after 24h (P<0.05), and reached to minimun after 72h (P<0.05). On the contrary, the expression of ARF6 increased after 12h, and the increase reached to the maximum after 72h (P<0.05). Furthermore, the vascular permeability increased gradually after 24h, and reached to the maximum after 72h (P<0.05) in high glucose group. Compared with the empty vector group, the over-expression of ROBO4 inhibited the expression of ARF6 significantly, and the FITC-Dextran permeability reduced obviously. Conclusion Over-expression of ROBO4 may significantly enhance the barrier functions of HRGEC in high glucose medium, and ROBO4 activation may be a potential therapeutic approach in diabetic nephropathy.
DOI: 10.11855/j.issn.0577-7402.2017.03.03
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