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Chun Luo

Publications and source records attributed to Chun Luo.

17 recordsLinked to original sources
PubMed2026

Integrative transcriptomic, spatial and functional-genomic analysis identifies a UFMylation-related vascular-stromal program and prioritizes WWTR1 in glioblastoma.

Glioblastoma (GBM) contains spatially organized stress-adaptive and vascular niches. Because transcript abundance does not measure UFM1 conjugation, we asked whether a UFMylation-related transcriptional axis identifies a reproducible tissue program and alters candidate prioritization. In 518 unique primary TCGA-GBM tumors profiled on the Affymetrix HT Human Genome U133A array, weighted gene co-expression network analysis of 8,000 variable genes yielded 12 modules. The 278-gene green module ranked first across nine prespecified traits (mean |r|=0.637). Direct overlap comprised 1/3 measurable UFMylation-core, 5/19 ER-stress/UPR, and 2/15 proteostasis genes; after excluding overlapping genes, correlations with the green eigengene remained significant (r = 0.373, 0.831, 0.639, and 0.699 for UFMylation-core, ER-stress/UPR, proteostasis, and composite scores, respectively). The green score was associated with overall survival per standard-deviation increase (HR 1.17, 95% CI 1.07-1.28), although clinical adjustment attenuated the estimate. In a 10-sample single-cell dataset, sample-level scores were higher in pericytes and endothelial cells than in malignant cells. Donor-aware IvyGAP analysis supported regional organization, whereas one Visium section showed stronger concordance with ER-stress/UPR and mesenchymal scores than with the UFMylation-core score. CellChat indicated pathway-selective rather than global remodeling of inferred vascular communication. Layer ablation moved WWTR1 from rank 48 using WGCNA alone to rank 4 overall and rank 1 among non-common-essential genes after cross-platform integration. These findings define an ER-stress/mesenchymal-weighted, UFMylation-related vascular-stromal transcriptional association and nominate WWTR1 for experimental testing.

Humans↗
PubMed2006

[Liposome-mediated glial growth factor 2 gene therapy in brain injury: an experimental study with rats].

OBJECTIVE: To explore the protective effect of glial growth factor-2 (GGF2) on brain injury. METHODS: Thirty-four SD rats underwent lateral fluid percussion to establish brain injury models and then were randomly divided into 4 groups: treatment group (n = 10, the plasmid pEGFP-N1-GGF2 mixed with liposome was injected into the brain tissue directly), vector control group (n = 10, the vector pEGFP-N1 mixed with liposome was injected into the brain tissue directly), liposome control group (n = 10, liposome was injected), and sham operation group (n = 4). Three assessment tasks were performed for neurobehavioral evaluation: Clivas Test, Beam Balance Test and Beam Walking Test. 10 days after brain injury, the rats were sacrificed and their brains were embedded in paraffin for HE staining, Nissle staining and immunohistochemical examination of MBP, NSE, and GFAP. RESULTS: The Clivas test score of the treatment group was 66.25 +/- 3.54, significantly higher than those of the vector control group and. liposome control group (58.31 +/- 3.72 and 57.21 +/- 3.93 respectively, both P < 0.05). The beam test score of the treatment group was 2.59 +/- 0.21, significantly lower than those the vector control group and liposome control group (3.41 +/- 0.25 and 3.24 +/- 0.22 respectively, both P < 0.05). The walking test score of the treatment group was 20.15 +/- 2.59, significantly lower than those of control group and liposome control group (27.00 +/- 3.47 and 27.80 +/- 3.00 respectively, both P < 0.05). The improvement in beam walking test was the greatest. The neuron number in the external granular layer and external pyramidal layer in cortex of the treatment group was 98 +/- 10, significantly more than those of the vector control group and liposome group (75 +/- 7 and 67 +/- 8, both P < 0.05). The neuron number in the internal pyramidal layer in cortex of the treatment group was 37 +/- 4, significantly more than those of the vector control group and liposome group (19 +/- 3 and 23 +/- 4 respectively, both P < 0.05). The neuron number in the CA1 region in hippocampus of the treatment group was 102 +/- 11, significantly more than those of the vector control group and liposome group (67 +/- 8 and 58 +/- 9 respectively, both P < 0.01). Higher level of immunoreactivity with MBP was also detected in the cortex in the rats of the treatment group. CONCLUSION: Cationic liposome-mediated GGF2 gene therapy effectively promotes the recovery of brain injury.

Animals↗
PubMed2006

Enhanced de novo neurogenesis and dopaminergic neurogenesis in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease-like mice.

Research reports on de novo neurogenesis, particularly dopaminergic (DA) neurogenesis in the adult mammalian substantia nigra (SN), remain very controversial. For this reason, we used the nestin second intron enhancer-controlled LacZ reporter transgenic mouse model coupled with the 1-methyl-4-phyenyl-1,2,3,6-tetrahydropyridine (MPTP) lesion system to investigate whether there are neurogenesis and DA neurogenesis in the SN of the adult normal and Parkinson's disease (PD)-like mice. First, we demonstrated the presence of neural progenitor cells (NPCs), basal levels of neurogenesis, and DA neurogenesis in the normal adult mouse SN. Second, we showed that there is not only a significant increase in the number of NPCs but also a dramatic increase of neurogenesis from the NPCs in the SN and the midline region adjacent to the SN of the PD-like mice compared with that of normal controls. More importantly, we also demonstrated that there is an increase of DA neurogenesis in the SN of the MPTP-lesioned mice. Third, we showed that the increased DA neurogenesis in the MPTP-lesioned mice was derived from the NPCs and 5-bromodeoxyuridine-positive cells, suggesting that multiple stem cell lineages may contribute to the enhanced neurogenesis in the adult SN. Taken together, these results establish that there are basal levels, albeit low, and increased levels of de novo neurogenesis and DA neurogenesis in the SN of the adult normal and PD-like mice, respectively. The increased NPCs in the MPTP-lesioned mice further suggest that experimental approaches to promote de novo neurogenesis may provide an effective therapy for PD by functional replacement of degenerated DA neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice.

Adult neural progenitor cells (NPCs) are an attractive source for functional replacement in neurodegenerative diseases and traumatic injury to the central nervous system (CNS). It has been shown that transplantation of neural stem cells or NPCs into the lesioned region partially restores CNS function. However, the capacity of endogenous NPCs in replacement of neuronal cell loss and functional recovery of spinal cord injury (SCI) is apparently poor. Furthermore, the temporal and spatial response of endogenous adult NPCs to SCI remains largely undefined. To this end, we have analyzed the early organization, distribution, and potential function of NPCs in response to SCI, using nestin enhancer (promoter) controlled LacZ reporter transgenic mice. We showed that there was an increase of NPC proliferation, migration, and neurogenesis in adult spinal cord after traumatic compression SCI. The proliferation of NPCs detected by 5-bromodeoxyuridine incorporation and LacZ staining was restricted to the ependymal zone (EZ) of the central canal. During acute SCI, NPCs in the EZ of the central canal migrated vigorously toward the dorsal direction, where the compression lesion is generated. The optimal NPC migration occurred in the adjacent region close to the epicenter. More significantly, there was an increased de novo neurogenesis from NPCs 24 hours after SCI. The enhanced proliferation, migration, and neurogenesis of (from) endogenous NPCs in the adult spinal cord in response to SCI suggest a potential role for NPCs in attempting to restore SCI-mediated neuronal dysfunction.

Animals↗
PubMed2005

[Molecular cloning and identify expression of the novel human LNX gene in gliomas].

OBJECTIVE: To clone and identify expression pattern of the novel LNX gene, and characterize its molecular mechanism in all grades of human gliomas. METHODS: From a fetal brain cDNA library, we isolated the novel human LNX gene. The expression pattern of LNX gene in 16 normal tissues was examined by MTC panel (Clontech). Microarray were adopted and hybridized with LNX probes to examine the expression of novel gene in gliomas. Northern hybridization was used for verifying expression of LNX gene in gliomas. Two-hybrid screen in yeast was used to identify human LNX interacting proteins. Pull-down assays and Co-immunoprecipitation were transfected in HEK293 cells according to the lipofectAMINE protocol. RESULTS: We isolated a 3.7 kb cDNA containing an open reading frame (ORF) of 1,899 bp and a putative 632 amino acids protein, which was located on 4q12. cDNA microarray showed LNX was down-regulated in all 18 glioma samples and it was testified by Northern-blot. The MTC panel showed a ubiquitous expression pattern which highly expressed in adult brain, kidney and pancreas, while weak expression in heart, lung, etc. The two-hybrid screen in yeast revealed that LNX interacted with SKIP (Ski interacting protein) via PDZ domains. The co-immunoprecipation suggested that LNX interacted with SKIP in HEK293 cells and could affect the subcellular localization of Numb, which indicated that LNX might function as a molecular anchor that localized Numb to the subcellular site of its interaction with Notch. CONCLUSION: cDNA microarray technology is a powerful technique in screening and locking differentially expressed genes in gliomas, LNX was closely related to human gliomas and suggested playing an important role in gliomas by notch signal approach.

Cloning, Molecular↗
PubMed2005

Motor neuron degeneration promotes neural progenitor cell proliferation, migration, and neurogenesis in the spinal cords of amyotrophic lateral sclerosis mice.

The organization, distribution, and function of neural progenitor cells (NPCs) in the adult spinal cord during motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remain largely unknown. Using nestin promoter-controlled LacZ reporter transgenic mice and mutant G93A-SOD1 transgenic mice mimicking ALS, we showed that there was an increase of NPC proliferation, migration, and neurogenesis in the lumbar region of adult spinal cord in response to motor neuron degeneration. The proliferation of NPCs detected by bromodeoxyurindine incorporation and LacZ staining was restricted to the ependymal zone surrounding the central canal (EZ). Once the NPCs moved out from the EZ, they lost the proliferative capability but maintained migratory function vigorously. During ALS-like disease onset and progression, NPCs in the EZ migrated initially toward the dorsal horn direction and then to the ventral horn regions, where motor neurons have degenerated. More significantly, there was an increased de novo neurogenesis from NPCs during ALS-like disease onset and progression. The enhanced proliferation, migration, and neurogenesis of (from) NPCs in the adult spinal cord of ALS-like mice may play an important role in attempting to repair the degenerated motor neurons and restore the dysfunctional circuitry which resulted from the pathogenesis of mutant SOD1 in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2005

Phosphorylation of serine residues in histidine-tag sequences attached to recombinant protein kinases: a cause of heterogeneity in mass and complications in function.

High-level recombinant expression of protein kinases in eukaryotic cells or Escherichia coli commonly gives products that are phosphorylated by autocatalysis or by the action of endogenous kinases. Here, we report that phosphorylation occurred on serine residues adjacent to hexahistidine affinity tags (His-tags) derived from several commercial expression vectors and fused to overexpressed kinases. The result was observed with a variety of recombinant kinases expressed in either insect cells or E. coli. Multiple phosphorylations of His-tagged full-length Aurora A, a protein serine/threonine kinase, were detected by mass spectrometry when it was expressed in insect cells in the presence of okadaic acid, a protein phosphatase inhibitor. Peptide mapping by liquid chromatography-mass spectrometry detected phosphorylations on all three serine residues in an N-terminal tag, alpha-N-acetyl-MHHHHHHSSGLPRGS. The same sequence was also phosphorylated, but only at a low level, when a His-tagged protein tyrosine kinase, Pyk2 was expressed in insect cells and activated in vitro. When catalytic domains of Aurora A and several other protein serine/threonine kinases were expressed in E. coli, serines in the affinity tag sequence GSSHHHHHHSSGLVPRGS were also variably phosphorylated. His-Aurora A with hyperphosphorylation of the serine residues in the tag aggregated and resisted thrombin-catalyzed removal of the tag. Treatment with alkaline phosphatase partly restored sensitivity to thrombin. The same His-tag sequence was also detected bearing alpha-N-d-gluconoylation in addition to multiple phosphorylations. The results show that histidine-tag sequences can receive complicated posttranslational modification, and that the hyperphosphorylation and resulting heterogeneity of the recombinant fusion proteins can interfere with downstream applications.

Acetylation↗
PubMed2005

False recognition across meaning, language, and stimulus format: conceptual relatedness and the feeling of familiarity.

Four experiments examined contributions of conceptual relatedness and feelings of familiarity to false recognition. Participants first studied lists of unrelated items (e.g., table, lock) followed by a recognition test with three types of items: (1) studied items (e.g., table), (2) semantically related lures (e.g., key), and (3) unrelated lures (e.g., cup). Participants falsely recognized more related than unrelated lures when the stimuli were words (Experiment 1A) and pictures (Experiment 1B), when the studied items and related lures differed in language (Experiment 2), and when they differed in perceptual format (Experiment 3). In Experiment 4, an attribution manipulation, designed to make feelings of familiarity nondiagnostic for memory judgments, eliminated the false-recognition effect obtained in Experiment 3. Overall, the study suggests that conceptual relatedness produces false recognition even in the absence of shared perceptual surface features between study and test items, and it does so by generating feelings of familiarity.

Attitude↗
PubMed2004

Molecular cloning and characterization of a novel human BTB domain-containing gene, BTBD10, which is down-regulated in glioma.

The broad-complex, tramtrack (ttk) and bric-a-brac/poxvirus and zinc finger proteins (BTB/POZ) domain is highly conserved in a large family of eukaryotic proteins and is crucial for the latter's diverse roles in mediating interactions among proteins that are involved in transcription regulation and chromatin structures. From a fetal brain cDNA library, we isolated a cDNA of 2489 base pairs (bp) encoding a novel human BTB domain-containing protein named BTBD10. The cDNA contained an open-reading frame (ORF) of 1428 bp encoding a putative 475-amino acid (aa) protein. The BTBD10 gene was located on human chromosome 11p15.2 and consisted of nine exons spanning about 75.2 kilobase pairs (kb) of the human genome. The cDNA microarray analysis showed that BTBD10 was down-regulated in all 18 glioma samples. The expression pattern of BTBD10 gene was examined by multiple tissue cDNA (MTC) panels (Clontech), which showed a ubiquitous expression pattern in the 16 tissues examined with high expression in adult brain, testis and small intestine and weak expression in the heart, lung, liver, kidney, pancreas, spleen, thymus, prostate, ovary and colon. The subcellular localization result revealed that BTBD10 was located specifically in the nucleus of HEK293 and COS7 cell lines, suggesting that it may function in transcriptional regulation. The different expression patterns of BTBD10 in different grades of glioma versus normal brain were also examined by RT-PCR and Northern blot. We also investigated the expression of BTBD10 in hepatocellular carcinoma, ovary cancer and lung cancer, and the results revealed no significant difference in these three tumors. All these data suggested that BTBD10 might play a role in glioma.

Adolescent↗
PubMed2004

Identification and characterization of NBEAL1, a novel human neurobeachin-like 1 protein gene from fetal brain, which is up regulated in glioma.

The Beige and Chediak-Higashi (BEACH) domain is highly conserved in a large family of eukaryotic proteins, and is crucial for their functions in vesicle trafficking, membrane dynamics and receptor signaling. From a fetal brain cDNA library, we isolated a cDNA of 3858 bp encoding a novel human BEACH protein, which was named as human neurobeachin-like 1 (NBEAL1) gene. The cDNA had an open reading frame (ORF) of 3006 bp encoding a putative 1001 amino acid protein. The NBEAL1 gene was located on human chromosome 2q33-2q34 and consisted of 25 exons spanning about 73 kb of the human genome. PSORT analysis indicated that the NBEAL1 protein contained a vacuolar-targeting motif ILPK, which suggested the protein might be located in the cell lysosome. The expression pattern was examined by reverse transcription/polymerase chain reaction (RT-PCR), which showed that the transcripts were highly expressed in the human brain, kidney, prostate, and testis while lowly in the ovary, small intestine, colon and peripheral blood leukocyte. In addition, the RT-PCR result of and Northern blot showed that the novel gene was highly expressed in the biopsies of different grade glioma, especially in that of lower grade ones, which suggested it might be correlative with the glioma.

Adolescent↗
PubMed2004

[Cluster analysis and identify significance of novel genes related to glioma in molecule classification].

OBJECTIVE: To screen differentially expressed genes in the development of human glioma and establish molecular classification of glioma preliminary based on gene expression using cDNA microarray. METHODS: Brain specimens were obtained from 18 patients with glioma, 10 males and 8 females, aged 14 approximately 62 with an average age of 44.4. The total RNAs of these glioma specimens and 2 specimens of donated brain of normal adults were extracted. BioStarH140S microarray (including 8347 old genes and 5592 novel genes) were adopted and hybridized with probes which were prepared from the total RNAs. Differentially expressed genes between the normal tissues and glioma tissues were assayed after scanning cDNA microarray with ScanArray 4000. Northern hybridization, and in situ hybridization (ISH) were used to identify the functions of novel genes. Those differentially expressed genes were studied with Hierarchical method and molecular classification of glioma was preliminarily carried out. RESULTS: Among the 13 939 target genes, there were 1200 (8.61%) differentially expressed genes and 395 (2.83%) novel genes. 348 genes were up-regulated and 852 genes were down-regulated in glioma. The results of bioinformatical analysis, Northern hybridization and ISH revealed that those novel genes were highly associated with glioma. There were multiple genes which were relevance to classification by Hierarchical method, such as MAP gene, cytoskeleton and matrix motility genes, etc. Molecular classification of glioma with Hierarchical cluster was in accordance with pathology and revealed internal essence in tumorigenesis and development. CONCLUSION: Multiple genes play important roles in development of glioma. cDNA microarray technology is a powerful technique in screening for differentially expressed genes between two different kinds of tissues.

Adolescent↗
PubMed2004

Cloning and characterization of a novel human cDNA encoding a J-domain protein (DNAJA5) from the fetal brain.

J-domain proteins are involved in protein importing and sorting, protein translocation into the endoplasmic reticulum and interaction with hsp70, cell cycle regulation and exocytosis. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone encoding a putative 531 amino acid protein with a DnaJ domain and C2H2-type zinc finger motif, which was named as DNAJA5 (human DnaJ homology subfamily A member 5). The putative protein of DNAJA5 gene was homologous to Caenorhabditis elegans DNJ-17 (identity 33.2% similarity 45.1%). By mapping, we located DNAJA5 gene to human chromosome 5p12-5p13. The DNAJA5 gene contained at least 12 exons that spanned more than 25.6 kb of the genomic sequence. The reverse transcription-polymerase chain reaction analysis indicated that it was expressed in the human brain, placenta, kidney and pancreas. DNAJA5 might play a role in co-operating with Hsp70.

Amino Acid Sequence↗
PubMed2003

VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SOD1-mediated motor neuron cell death.

The increased oxidative stress induced by mutant SOD1 is associated with motor neuron degeneration in both human ALS and transgenic mice expressing mutant SOD1. Vascular endothelial growth factor (VEGF) is neurotrophic and also protects from hypoxia-induced neuronal injury. The potential role of VEGF in preventing mutant SOD1-mediated motor neuron cell death was examined using a mouse NSC34 motor neuron-like cell culture system. Infection with adenovirus containing mutant G93A-SOD1, but not vector control or wild-type SOD1, increased cellular oxidative stress and motor neuron-like cell death. However, NSC34 cells pretreated with VEGF displayed a dose-dependent resistance to oxidative damage from hydrogen peroxide, TNF-alpha, and mutant G93A-SOD1. VEGF activated both PI3-K and MAPK activities in mouse NSC34 motor neuron-like cells. Pharmacological inhibitors and constitutively active as well as dominant negative mutants of MAPK and PI3-K revealed that the protective effects of VEGF were mediated via the PI3-K activity, and that MAPK activation was not associated with NSC34 cell survival. Furthermore, VEGF-induced downstream Akt activation promoted motor neuron-like NSC34 cell survival in the presence of mutant G93A-SOD1. Thus, VEGF protected mouse NSC34 motor neuron-like cell death from mutant G93A-SOD1 effects via PI3-K/Akt activation.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Spatial and temporal profile of apoptosis following lateral fluid percussion brain injury.

OBJECTIVE: To investigate the spatial and temporal profile of neural cell apoptosis following traumatic brain injury (TBI). METHODS: In addition to morphological evidence of apoptosis, TUNEL histochemistry assay was used to identify DNA fragmentation in situ at both light and electron microscopic levels, whereas characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. RESULTS: Using TUNEL method, we detected massive cells with extensive DNA fragmentation in different regions of the brains of rats subjected to experimental traumatic brain injury. Compared with the sham controls, in the injured cortex, the apoptotic cells were detectable for up to 24 h and reached a peak at 1 week after injury. The number of apoptotic cells in the white matter h ad a significant increase as early as 12 h after injury and peaked at 1 wee k. The number of apoptotic cells increased in the hippocampus at 72 h, whereas i n the thalamus, the peak of apoptotic cells was at 2 weeks after injury. The number of apoptotic cells in most regions returned to sham values 2 months after in jury. Gel electrophoresis of DNA extracted from affected areas of the injured br ain revealed only internucleosomal fragmentation at 185-bp intervals, a feature originally described in apoptotic cell death. And no DNA ladder was detectable in the cortex and hippocampus contralateral to the injured hemisphere. CONCLUSIONS: These data suggest that in addition to the well described necrotic cell death, a temporal course of apoptotic cell death is initiated after brain trauma in selected brain regions.

Analysis of Variance↗
PubMed2002

Changes of bcl-x(L) and bax mRNA expression following traumatic brain injury in rats.

OBJECTIVE: To investigate the changes of bcl-2 gene family and the molecular mechanism of neuronal apoptosis following traumatic brain injury (TBI) in rats. METHODS: Male Sprague-Dawley (SD) rats were subjected to lateral fluid percussion brain injury (FPBI) of moderate severity. The bcl-x(L) and bax mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). In addition to morphological evidence of apoptosis, terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labeling (TUNEL) histochemistry was used to identify the DNA fragmentation in situ at both light and electron microscope levels, whereas characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. RESULTS: The apoptotic response to trauma was regionally distinct and may be involved in both acute and delayed cell death. The bcl-x(L) mRNA expression of the impact site was significantly lower (67.42%+/-7.54%) than that of the ipsilateral hemisphere at 6 hours after injury (P<0.01). The decrease of bcl-x(L) mRNA expression preceded apoptosis at 24 hours after injury. The bax mRNA expression rose slowly, doubled at 3 days after injury and returned to the sham level slowly. CONCLUSIONS: Decreased expression of bcl-x(L) mRNA and increased expression of bax mRNA coincides with apoptosis following brain injury. The bcl-2 gene family is involved in neuronal apoptosis after TBI, and the changes of mRNA expression of the family members lead the neuronal cells to apoptosis.

Animals↗
PubMed1999

Alterations of bcl-2, bcl-x and bax protein expressions in area CA-3 of rat hippocampus following fluid percussion brain injury.

OBJECTIVE: To investigate the alterations of bcl-2 gene family in the area of CA-3 in rats and the molecular mechanism of neuronal apoptosis following traumatic brain injury. METHODS: To investigate the alterations of bcl-2 gene family in the area of CA-3 in rats and the molecular mechanism of neuronal apoptosis following traumatic brain injury. RESULTS: The immunoreactivity of bcl-2 and bcl-x proteins decreased in the hippocampus ipsilateral impact site at 6 hours after injury, and this was the main cause of down-regulation of the value of (bcl-2+bcl-x)/ bax. During the period of 1-3 days after injury, bax protein expression increased significantly, while bcl-2 and bcl-x protein expressions decreased relatively slowly. The decreased value of (bcl-2+bcl-x)/ bax was mainly due to the bax up-regulation. CONCLUSIONS: The bcl-2 gene family is involved in neuronal apoptosis after traumatic brain injury, and the protein-expression alterations of the bcl-2 gene family members lead to apoptosis of the neuronal cells.

Journal Article↗