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Liposomal Honokiol induces ROS-mediated apoptosis via regulation of ERK/p38-MAPK signaling and autophagic inhibition in human medulloblastoma

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Signal Transduction and Targeted Therapy 2022年第3期7卷 625-627页

作者： Shenglan Li Jinyi Chen Yaqiong Fan Ce Wang Can Wang Xiaohong Zheng Feng Chen Wenbin Li Department of neuro-oncology Cancer CenterBeijing Tiantan HospitalCapital Medical UniversityBeijingChina

Dear Editor,Nowadays,medulloblastoma accounts for approximately 25% of all pediatric brain tumors.1 Even with the successful treatment of primary tumors,there are still serious side ***(HNK)is defined as small bisphen... 详细信息

关键词： tumors pediatric Lipo

Neutrophil extracellular traps mediate neuro-immunothrombosis

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Neural Regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo Lou Jianning Zhang Quanjun Deng Xin Chen Department of neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin neurological Institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry *** extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation ***,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and *** summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic *** blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological *** research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of ***,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain *** review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

Presence of c.3956del C mutation in familial adenomatous polyposis patients from Brazil

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World Journal of Gastroenterology 2015年第31期21卷 9413-9419页

作者： Caroline Aquino Moreira-Nunes Diego di Felipe ávila Alcantara Sérgio Figueiredo Lima-Júnior Sandro Roberto de Araújo Cavalléro Juan Antonio Rey Giovanny Reboucas Pinto Paulo Pimentel de Assumpcao Rommel Rodriguez Burbano Biological Science Institute Federal University of Pará Nucleus of Research in Oncology Federal University of Pará Molecular neuro-oncogenetics Laboratory Research Unit-Unidad de InvestigaciónHospital Universitario La Paz Genetics and Molecular Biology Laboratory Federal University of Piaui

AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP,family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the Jo?o de Barros Barreto University Hospital(Belem,Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations,Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records,it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene,and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP,family members without disease symptoms showed the mutation in the APC gene. In the present study,we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956 del C mutation was found in all families from this study,and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration(i.e.,a de novo mutation that arose

关键词： Familial adenomatous polyposis APC Torrent sequencing Colorectal cancer

Regulation of autophagic flux by CHIP

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neuroscience Bulletin 2015年第4期31卷 469-479页

作者： Dongkai Guo Zheng Ying Hongfeng Wang Dong Chen Feng Gao Haigang Ren Guanghui Wang Laboratory of Molecular neuropathology Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical SciencesSoochow University

Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic flux is present in many pathological conditions including neurodegeneration and tumors. CHIP/STUB1, an E3 ligase, plays an important role in neurodegeneration. In this study, we identified the regulation of autophagic flux by CHIP （carboxy-terminus of HscT0-interacting protein）. Knockdown of CHIP induced autophagosome formation through increasing the PTEN protein level and decreasing the AKT/mTOR activity as well as decreasing phosphorylation of ULK1 on Ser757. However, degradation of the autophagic substrate p62 was disturbed by knockdown of CHIP, suggesting an abnormality of autophagic flux. Furthermore, knockdown of CHIP increased the susceptibility of cells to autophagic cell death induced by bafilomycin AI. Thus, our data suggest that CHIP plays roles in the regulation of autophagic flux.

关键词： CHIP/STUB1 autophagic flux neuro-degeneration mTOR AKT

Disorder of blood-aqueous barrier following Ahmed Glaucoma Valve implantation

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Chinese Medical Journal 2013年第6期126卷 1119-1124页

作者： ZHOU Min-wen WANG Wei CHEN Shi-da HUANG Wen-bin ZHANG Xiu-lan Department of Glaucoma Sun Yat-sen University Guangzhou Guangdong 520275 China Department of neuro-ophthalmology Sun Yat-sen University Guangzhou Guangdong 520275 China Zhongshan Ophthalmic Center State Key Laboratory of ophthalmology Sun Yat-sen University Guangzhou Guangdong 520275 China

Background Ahmed Glaucoma Valve implantation （AGVI） is blood-aqueous barrier （BAB） has been noted after some surgica BAB disruption afterAGVl. used to treat refractory glaucoma. Breakdown of the techniques. The current study was designed to assess Methods Anterior chamber protein content was measured by the laser flare cell photometry in 22 eyes of 22 patients with refractory glaucoma before AGVI and at each postoperative visit up to 1 month. Results Before AGVI the mean aqueous flare values in all eyes were （15.17＋9.84） photon counts/ms. After AGVI, the values significantly increased at day 1, day 3, and week I compared to those before AGVI （all P 〈0.05） with a peak at day 3. They returned to pre-operative levels at week 2, and were lower than preoperative level at month 1. Eyes with previous intraocular surgery history had greater aqueous flare values than those without previous intraocular surgery history, but there were no significant differences at all time points postoperatively （all P 〉0.05）. Furthermore, eyes with shallow anterior chambers had greater aqueous flare values at day 3 and week 1 （all P 〈0.05）. When comparing eyes with other refractory glaucoma conditions, neovascular glaucoma combined with intravitreal bevacizumab injection resulted in lower aqueous flare values after AGVI, but no significant differences were observed at all time points, postoperatively （all P 〉0.05）. Conclusions The BAB was impaired and inflammation was present in the anterior chamber in refractory glaucomatous eyes following AGVI. However, such conditions were resolved within 1 month postoperatively. Intravitreal bevacizumab treatment in neovascular glaucoma eyes before AGVI may prevent BAB breakdown.

关键词： aqueous flare blood-aqueous barrier Ahmed Glaucoma Valve implantation

siRNA epidermal growth factor receptor silencing in U251 glioma cells

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Neural Regeneration Research 2008年第6期3卷 652-655页

作者： Chunsheng Kang Zhiyong Zhang Zhifan Jia Qiang Huang Guangxlu Wang Mingzhe Qiu Peiyu Pu Department of neurosurgery Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology Tianjin Neurological Institute Tianjin 300052 China

BACKGROUND： Dicer, a large multidomain ribonuclease, is responsible for processing double-stranded RNAs （dsRNAs） to 20-bp-long small interfering RNAs （siRNAs）, which act as effectors during RNA interference （RNAi）. OBJECTIVE： To observe the efficacy of siRNA cocktails generated by recombinant human Dicer on the down-regulation of epidermal growth factor receptor （EGFR） expression in human glioma cells. DESIGN, TIME AND SETTING： The following in vitro experiment was performed at the Department of neurosurgery, Tianjin Medical University General Hospital and Laboratory of neuro-Oncology, Tianjin neurological Institute. MATERIALS： Mini-RNA isolation kit, human placenta complimentary DNA （cDNA） was produced by Tiangen Biotech （Beijing, China）, human glioblastoma U251-MG cells were produced by the Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. METHODS： A PCR product from the human EGFR, which corresponded to the tyrosine kinase domain of the 3＇-end fragment, was used as the T7-promotor for in vitro transcription. siRNA cocktails were generated by in vitro dicing of double stranded RNA. A total of 500, 250 and 125 μg siRNA cocktails were transiently transfected into U251 glioma cells through the use of the GeneSilencer. MAIN OUTCOME MEASURE： Expression of EGFR was detected by real-time PCR. RESULTS： The total PCR product of the human EGFR, corresponding to the tyrosine kinase domain, is approximately 680 bp in length. The PCR transcriptants included GCC leader sequences and a T7 promoter sequence, with a fragment of EGFR cDNA at the center. The T7 promoter was prepared for in vitro transcription of dsRNA. After dicing for 24 hours, the 21-nt siRNA cocktails were verified by 4% agarose gel. The difference between threshold cycle of a sample assay and threshold cycle of the corresponding endogenous reference （ΔCt） among parental U251 cells and cells transfected with different doses of siRNA cocktails were determined to be 3.06, 7.35, and 10.31 cycl

关键词： siRNA epidermal growth factor receptor, glioma gene expression

The effect of umbrella-type branching on the blood circulation and tumor targeting of star-branched PLA-PMPC copolymer micelles

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Science China(Technological Sciences) 2021年第1期64卷 71-82页

作者： LONG LiXia CHENG LinJie HOU JingJing WANG LiMei WANG Xu HE LiGang LI SiDi ZHAO Jin HOU Xin KANG ChunSheng YUAN XuBo Tianjin Key Laboratory of Composite and Functional Materials School of Materials Science and EngineeringTianjin UniversityTianjin 300072China Department of neurosurgery Tianjin Medical University General HospitalLab of Neuro-oncologyTianjin Neurological InstituteKey Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjin 300052China

The effect of branching on the blood circulation and tumor targeting of polymer nanovehicles in vivo was investigated in this study. For the purpose, star-branched poly(lactic acid) and poly(2-methacryloyloxyethyl phosphorylcholine)(PLA-PMPC)copolymers with umbrella-type AB3,(AB3)_(2), and(AB3)_(3) architecture were synthesized by branching at the PLA core. Micelles self-assembled from these copolymers were used to evaluate the effect of core branching on blood circulation and tumor targeting. The results showed that branching changed the behavior of polymeric self-assembly in solution, thereby changing the size and surface anti-fouling performance of the polymeric micelles. Moreover, star-branched copolymer micelles with a higher branching degree allowed their payload to persist better in blood(half-time prolonged from 7.1, 8.6 to 13.8 h) and for a 1.72-fold higher content at the tumor site. These studies suggest that raising the branching degree of amphiphilic copolymer potentially offers a promising strategy for the design of carriers capable of enhanced circulation and targeting in vivo.

关键词： umbrella-type branching star-branched copolymers anti-fouling prolonged circulation

Activity-dependent remodeling of genome architecture in engram cells facilitates memory formation and recall

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Neural Regeneration Research 2022年第5期17卷 991-993页

作者： Asaf Marco neuro-Epigenetics Laboratory the Robert H.Smith Faculty of FoodEnvironment and Agriculturethe Hebrew University of JerusalemRehovol CampusIsrael

The formation and preservation of longterm memories critically depend upon coordinated activity of neuronal circuits,intracellular signaling cascades and synaptic remodeling(Josselyn et al.,2015).These essential proce... 详细信息

关键词： remodeling ngram

Nonmetabolic functions of metabolic enzymes in cancer development

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Cancer Communications 2018年第1期38卷 677-683页

作者： Sean Lu Yugang Wang Brain Tumor Center and Department of neuro-Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

Metabolism is a fundamental biological process composed of a series of reactions catalyzed by metabolic *** evidence demonstrates that the aberrant signaling in cancer cells induces nonmetabolic functions of meta-bolic enzymes in many instrumental cellular activities,which involve metabolic enzyme-mediated protein post-trans-lational modifications,such as phosphorylation,acetylation,and *** the most well-researched literatures,metabolic enzymes phosphorylate proteins rather than their metabolites as *** metabolic enzymes have altered subcellular localization,which allows their metabolic products to directly participate in nonmetabolic *** review discusses how these findings have deepened our understanding on enzymes originally classi-fied as metabolic enzymes,by highlighting the nonmetabolic functions of several metabolic enzymes responsible for the development of cancer,and evaluates the potential for targeting these functions in cancer treatment.

关键词： Metabolic enzymes Function Protein kinase Metabolite products Phosphorylation Acetylation Succinylation Mitochondria