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Identification of TMEM159 as a biomarker of glioblastoma progression based on immune characteristics

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BIOCELL 2024年第8期48卷 1241-1263页

作者： JI SHI YE ZHANG YI CHEN TANGJUN GUO HAOZHE PIAO Graduate School Dalian Medical UniversityDalian116000China department of neurosurgery Liaoning Cancer Hospital&InstituteShenyang110042China department of neurosurgery Affiliated Hospital of Xuzhou Medical UniversityXuzhou221000China

Background:Glioblastoma multiforme(GBM)is the most general malignancy of the primary central nervous system that is characterized by high aggressiveness and *** protein 159(TMEM159)is an endoplasmic reticulum protein that can form oligomers with *** TMEM159-seipin complex decides the site of lipid droplet(LD)formation,and the formation of LDs is a marker of ***,the role of TMEM159 in the progression of GBM has not been investigated to ***:In this study,we examined the genes that may be associated with patient prognosis in GBM by bioinformatics analyses,and identified the key genes that affect the development of GBM using single-cell RNA sequencing *** biological functions of TMEM159 in GBM cells were additionally assessed by clone formation and transwell assays as well as using a model of chick embryo chorioallantois membrane(CAM)and western *** association between TMEM159 and epidermal growth factor receptor(EGFR)was finally analyzed in GBM ***:A prognostic model was established and validated for predicting the *** curve analysis showed a critical difference in the prognosis of the high-and low-risk groups predicted by the prognostic *** results demonstrated that TMEM159 affected the proliferation and invasion of GBM *** chick embryo CAM assays demonstrated that the inhibition of TMEM159 expression reduced angiogenesis in the CAM ***:The prognostic model achieved good predictive potential for high-risk *** findings also revealed that TMEM159 might be an important prognostic factor for GBM,indicating that the protein may be a promising therapeutic target for suppressing the development of GBM.

关键词： Single-cell RNA sequencing Glioblastoma TMEM159 EGFR Angiogenesis

The antitumor effects of Newcastle disease virus on glioma

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BIOCELL 2019年第3期43卷 119-127页

作者： JI SHI PEIXIN SUN YE ZHANG BING YAO HAOZHE PIAO department of neurosurgery Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital&InstituteShenyang110042China

Glioma is the most common primary malignant brain tumor with a poor survival *** recent years,no significant progress has been made in the treatment of gliomas in contrast to the development of improved diagnosis via molecular *** disease virus(NDV),a negative-stranded RNA virus that exhibits oncolytic activity,has been investigated for its capacity to elicit antitumor activity in many types of cancers,including ***,application of oncolytic viruses,such as NDV,as a new treatment strategy to specifically target aberrant signaling in glioblastomas has brought new *** many years,NDV has been investigated for its in vivo and in vitro efficacy in the treatment of various tumor *** on its safety in humans,specificity for tumor cells,and immunostimulatory properties,NDV represents a promising antitumor *** this review,we summarize the background of NDV and the antitumor mechanisms of NDV-mediated oncolysis,discuss the potential value and role of NDV in gliomas,and describe new advances and perspectives for future research.

关键词： Apoptosis Autophagy Immune response Oncolytic virus RAC1

The effect of aneurismal-wall mechanical properties on patient-specific hemodynamic simulations:two clinical case reports

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Acta Mechanica Sinica 2009年第5期25卷 677-688页

作者： Jialiang Chen Shengzhang Wang Guanghong Ding Xinjian Yang Haiyun Li department of Mechanics and Engineering Science Fudan University 200433 Shanghai China Beijing institute of neurosurgery 100050 Beijing China department of Biomedical Engineering Capital Medical University 100050 Beijing China

Hemodynamic factors such as the wall shear stress play an important role in the pathogenesis and treatment of cerebral aneurysms. In present study, we apply computational fluid-structure interaction analyses on cerebral aneurysms with two different constitutive relations for aneurismal wall in order to investigate the effect of the aneurismal wall mechanical properties on the simulation results. We carry out these analyses by using two patient-specific models of cerebral aneurysms of different sizes located in different branches of the circle of Willis. The models are constructed from 3D rotational angiography image data and blood flow dynamics is studied under physiologically representative waveform of inflow. From the patient models analyzed in this investigation, we find that the deformations of cerebral aneurysms are very small. But due to the nonlinear character of the Navier-Stokes equations, these small deformations could have significant influences on the flow characteristics. In addition, we find that the aneurismal-wall mechanical properties have great effects on the deformation distribution of the aneurysm, which also affects the wall shear stress distribution and flow patterns. Therefore, how to define a proper constitutive relation for aneurismal wall should be considered carefully in the hemodynamic simulation.

关键词： Intracranial aneurysm - Fluid-structure interaction Computational fluid dynamics Hemodynamics

Suicide transport blockade of motor neuron survival generates a focal graded injury and functional deficit

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Neural Regeneration Research 2021年第7期16卷 1281-1287页

作者： Allison S.Liang Joanna E.Pagano Christopher A.Chrzan Randall D.McKinnon department of neurosurgery Rutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA Member The Cancer Institute of New JerseyNew BrunswickNJUSA

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small *** axonal transport of a pro-apoptotic phosphatidylinosotol 3'-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug *** neuron loss was detected by choline acetyltransferase(ChAT) immunostaining and with a transgenic thy1-eGFP *** short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus *** quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 μg wortmannin, relative to sham controls, and remained low after 90 *** effects were observed with 200 ng and 100 ng *** also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 *** mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit *** rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 *** the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and *** efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral *** procedures were performed at Rutgers under established Institutional Animal Care and Use protocols(eIACUC_TR201800022, approved on March 20, 2018).

关键词： amyotrophic lateral sclerosis injury motor function motor neuron PI3'kinase sciatic nerve suicide transport wortmannin

EFFECTS OF PARENT ARTERY SEGMENTATION AND ANEURISMALWALL ELASTICITY ON PATIENT-SPECIFIC HEMODYNAMIC SIMULATIONS

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Journal of Hydrodynamics 2011年第5期23卷 660-668页

作者： CHEN Jia-liang DING Guang-hong YANG Xin-jian LI Hai-yun department of Mechanics and Engineering Science Fudan University Shanghai 200433 China Beijing institute of neurosurgery Beijing 100050 China department of Biomedical Engineering Capital Medical University Beijing 100050 China

It is well known that hemodynamics and wall tension play an important role in the formation, growth and rupture of aneurysms. In the present study, the authors investigated the influence of parent artery segmentation and aneurismal-wall elasticity on patient-specific hemodynamic simulations with two patient-specific cases of cerebral aneurysms. Realistic models of the aneurysms were constructed from 3-D angiography images and blood flow dynamics was studied under physiologically representative waveform of inflow. For each aneurysm three computational models were constructed： Model 1 with more extensive upstream parent artery with the rigid arterial and aneurismal wall, Model 2 with the partial upstream parent artery with the elastic arterial and aneurismal wall, Model 3 with more extensive upstream parent artery with the rigid wall for arterial wall far from the aneurysm and the elastic wall for arterial wall near the aneurysm. The results show that Model 1 could predict complex intra-aneurismal flow patterns and wall shear stress distribution in the aneurysm, but is unable to give aneurismal wall deformation and tension, Model 2 demonstrates aneurismal wall deformation and tension, but fails to properly model inflow pattern contributed by the upstream parent artery, resulting in local misunderstanding Wall Shear Stress （WSS） distribution, Model 3 can overcome limitations of the former two models, and give an overall and accurate analysis on intra-aneufismal flow patterns, wall shear stress distribution, aneurismal-wall deformation and tension. Therefore we suggest that the proper length of extensive upstream parent artery and aneurismal-wall elasticity should be considered carefully in establishing computational model to predict the intra-aneurismal hemodynamic and wall tension.

关键词： cerebral aneurysm fluid-structure interaction upstream parent artery wall tension hemodynamics

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

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World Journal of Methodology 2025年第1期15卷 72-79页

作者： Serdar Kabatas ErdinçCivelek Eyüp Can Savrunlu Umut Karaaslan Özlem Yıldız Erdal Karaöz department of neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of Pediatric Allergy-Immunology Institute of Health Sciences Marmara UniversityIstanbul 34865Türkiye Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye department of Child and Adolescent Psychiatry University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of Child and Adolescent Psychiatry Kocaeli University Faculty of MedicineKocaeli 41001Türkiye Center for Regenerative Medicine and Stem Cell Research&Manufacturing Liv HospitalIstanbul 34340Türkiye department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted *** recent studies,neuroinflammation and immune dysregulation have come to the forefront in its *** are studies suggesting that stem cell therapy may be effective in the treatment of *** To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell *** A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with *** The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor *** serious side effects were encountered during the 2-year *** The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

关键词： Autism spectrum disorder Neurorehabilitation Stem cell transplantation Wharton jelly mesenchymal stem cells Inflammation

PATIENT-SPECIFIC BLOOD DYNAMIC SIMULATIONS IN ASSESSING ENDOVASCULAR OCCLUSION OF INTRACRANIAL ANEURYSMS

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Journal of Hydrodynamics 2009年第2期21卷 271-276页

作者： CHEN Jia-liang WANG Sheng-zhang DING Guang-hong YANG Xin-jian LI Hai-yun department of Mechanics and Engineering Science Fudan University Shanghai 200433 China Beijing institute of neurosurgery Beijing 100050 China department of Biomedical Engineering Capital Medical University Beijing 100050 China

According to recent studies, there are various potential predictors for surgical outcome for cerebral aneurysms. An accurate surgical outcome assessment would help make better-informed decisions and avoid the risk of rebleeding. It is well known that hemodynamic factors play an important role in the pathogenesis and treatment of intracranial aneurysms. In this article, a computational fluid dynamic analysis is applied to one patient-specific model of the cerebral aneurysm located at the tip of basilar artery, by which the differences of hemodynamic parameters before and after endovascular treatment may be evaluated. Based on the model, we show that the flow behavior near the neck of the aneurysm sees great differences after endovascular treatment as compared with that before treatment, which also affects the wall shear stress and the displacement distribution. In addition, our whole simulation process is based on a series of CFD commercial software packages, which are easily available for doctors to implement such a method in their daily practice. These results would be used to assess the outcome of endovascular treatment for the aneurysm occlusion.

关键词： hemodynamics numerical simulation intracranial aneurysm

Role of the tumor microenvironment in shaping IDH-wildtype glioma plasticity,and potential therapeutic strategies

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Cancer Biology & Medicine 2022年第10期19卷 1423-1427页

作者： Lingxiang Wu Ruichao Chai Zheng Zhao Qianghu Wang Tao Jiang department of Bioinformatics Nanjing Medical UniversityNanjing 211166China institute for Brain Tumors Jiangsu Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China department of Molecular neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China Chinese Glioma Genome Atlas Network(CGGA) Beijing 100070China department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

Diffuse glioma is the most common primary malignant brain tumor in ***,the prognosis of glioma remains dismal,and almost all patients with glioma experience recurrence even after comprehensive treatment including maximal surgical resection,radiotherapy,and/or *** can be stratified according to their IDH mutation *** we have previously reported2,3,the genetic characteristics,pathogenesis,and chemotherapy response are distinct between IDH-mutant and IDH-wildtype *** instance,IDH-wildtype tumors are associated with poor prognosis and frequently have genomic alterations,including a gain of chromosome 7 and loss of chromosome *** tumors often show findings including CpG island hypermethylation and MET alterations.

关键词： glioma chemotherapy IDH

Local inhibition of matrix metalloproteinases reduced M2 macrophage activity and impeded recovery in spinal cord transected rats after treatment with fibroblast growth factor-1 and nerve grafts

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Neural Regeneration Research 2018年第8期13卷 1447-1454页

作者： Chuan-Wen Chiu Wen-Hung Huang Huai-Sheng Kuo May-Jywan Tsai Ching-Jung Chen Meng-Jen Lee Henrich Cheng department and institute of Pharmacology National Yang-Ming University Taipei Taiwan China Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans General Hospital Taipei Taiwan China department of Applied Chemistry Chaoyang University of Technology Taichung Taiwan China Center for Neural Regeneration Department of Neurosurgery Neurological Institute Taipei Veterans General Hospital Taipei Taiwan China

Alternatively activated macrophages （M2 macrophages） promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited more M2 macrophages and improved partial functional recovery in spinal cord transected rats. The migration of macrophages is matrix metalloproteinase （MMP） dependent. We used a general inhibitor of MMPs to influence macrophage migration, and we examined the migration of macrophage populations and changes in spinal function. Rat spinal cords were completely transected at Ts, and 5 mm of spinal cord was removed （group T）. In group R, spinal cord-transected rats received treatment with fibroblast grow th factor- 1 and peripheral nerve grafts. In group RG, rats received the same treatment as group R with the addition of 200 μM GM6001 （an MMP inhibitor） to the fibrin mix. We found that MMP-9, but not MMP- 2, was upregulated in the graft area of rats in group R. Local application of the MMP inhibitor resulted in a reduction in the ratio of arginase-1 （M2 macrophage subset）/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was applied at 8 weeks postoperation, the partial functional recovery observed in group R was lost. This effect was accompanied by a decrease in brain-derived neurotrophic factor levels in the nerve graft. These results suggested that the arginase-1 positive population in spinal cord transected rats is a migratory cell population rather than the phenotypic conversion of early iNOS^＋ cells and that the migration of the arginase-1^＋ population could be regulated locally. Simultaneous application of MMP in- hibitors or promotion of MMP activity for spinal cord injury needs to be considered if the coadministered treatment involves M2 recruitment.

关键词： spinal cord injury fibroblast growth factor-1 matrix metalloproteinase GM6001 macrophage