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1.
Neoplasma ; 70(4): 534-544, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37789777

ABSTRACT

Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.


Subject(s)
Glioma , Mitogen-Activated Protein Kinases , Animals , Mice , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glioma/pathology , MAP Kinase Signaling System , Mice, Nude , Mitogen-Activated Protein Kinases/metabolism , Neoplasm Invasiveness/genetics , Signal Transduction , Humans
2.
CNS Neurosci Ther ; 29(2): 525-537, 2023 02.
Article in English | MEDLINE | ID: mdl-36513959

ABSTRACT

AIMS: New thrombectomy strategies have emerged recently. Differences between posterior circulation stroke management via aspiration and stent retriever remain to be evaluated. We compared the safety and efficacy of aspiration and stent retriever in treating posterior circulation stroke. METHODS: Three databases (PubMed, Embase, and Cochrane Library) were systematically searched for studies comparing aspiration and stent retriever in patients with posterior circulation stroke. The modified Newcastle-Ottawa scale was used to assess the risk of bias. A random-effects model was used. RESULTS: Fifteen cohort studies with 1451 patients were included. Pooled results showed a significant difference in total complication (odds ratio [OR] 0.48, 95% confidence interval [CI] [0.30, 0.76], p = 0.002). successful recanalization (1.85, [1.30, 2.64], p = 0.0006), favorable outcome (1.30, [1.02, 1.67], p = 0.04), procedure duration (-22.10, [-43.32, -0.88], p = 0.04), complete recanalization (4.96, [1.06, 23.16], p = 0.009), and first-pass effect (2.59, [1.55, 4.32], p = 0.0003) between the aspiration and stent retriever groups, and in favor of aspiration. There was no significant difference in the outcomes of rescue therapy (1.42, [0.66, 3.05], p = 0.37) between the two groups. CONCLUSION: Patients with posterior circulation stroke receiving treatment with aspiration achieved better recanalization, first-pass effect, and shorter procedure time. Aspiration may be more secure than a stent retriever.


Subject(s)
Brain Ischemia , Endovascular Procedures , Stroke , Humans , Endovascular Procedures/methods , Retrospective Studies , Stents , Stroke/surgery , Thrombectomy/methods , Treatment Outcome
7.
FEBS Lett ; 576(3): 481-6, 2004 Oct 22.
Article in English | MEDLINE | ID: mdl-15498584

ABSTRACT

Introns are present in some human pre-tRNAs. They are spliced out during the maturation processes of pre-tRNAs in a way that is irrelevant to their specific nucleotide sequences. This unique characteristic of tRNA splicing can be used for generation of small antisense RNAs by replacing the intron sequences with corresponding antisense sequences. In this work, the intron sequence of human pre-tRNAtyr gene was replaced with a 20 bp antisense sequence targeted to the 5' coding region of cyclin D1, a molecule that was over-expressed in many malignant proliferating cells. Under the control of U6 SnRNA promoter to further enhance transcription efficiency of the modified pre-tRNAtyr gene and subsequent antisense generation, the antisense RNA exhibited obvious suppression of cyclin D1 expression in H22 hepatoma cells. The growth of H22-transplanted tumors in mice was significantly inhibited when treated with naked plasmid DNA harboring the cyclin D1 antisense RNA generating cassette. Such tumor growth inhibition might be due to apoptosis caused by reduced cyclin D1 expression as revealed by immunohistochemical analysis of tumor samples.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cyclin D1/genetics , Liver Neoplasms/pathology , RNA Precursors/genetics , RNA Splicing/genetics , RNA, Antisense/genetics , Alternative Splicing/genetics , Animals , Base Sequence , Carcinoma, Hepatocellular/genetics , Cell Division , Cell Line, Tumor , DNA, Ribosomal/genetics , Humans , Liver Neoplasms/genetics , Mice , Molecular Sequence Data , Oligodeoxyribonucleotides , RNA, Transfer, Tyr/genetics , Transcription, Genetic , Transplantation, Heterologous
8.
J Mol Biol ; 341(1): 271-9, 2004 Jul 30.
Article in English | MEDLINE | ID: mdl-15312778

ABSTRACT

Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.


Subject(s)
Severe acute respiratory syndrome-related coronavirus/metabolism , Viral Proteins/metabolism , Animals , Chlorocebus aethiops , Disulfides/metabolism , Humans , Membrane Glycoproteins/metabolism , Phylogeny , Proteomics , Severe acute respiratory syndrome-related coronavirus/chemistry , Severe acute respiratory syndrome-related coronavirus/genetics , Sequence Analysis, Protein , Spike Glycoprotein, Coronavirus , Vero Cells , Viral Envelope Proteins/metabolism , Viral Proteins/chemistry , Viral Proteins/genetics , Viroporin Proteins
9.
Wei Sheng Wu Xue Bao ; 44(6): 711-6, 2004 Dec.
Article in Chinese | MEDLINE | ID: mdl-16110944

ABSTRACT

To screen small animals susceptible to SARS-CoV, five species of animals, including guinea pig, hamster, albino hamster, chicken and rat, were experimentally infected with SARS-CoV strain BJ-01 by different routes. On the basis of this, further cynomolgus and rhesus macaques were selected and experimentally inoculated SARS-CoV, the quality they serve as animal model for SARS was evaluated. The results showed that, all five species of small animals chosed were not susceptible to SARS-CoV, no characterized changes in clinical sign and histopathology were observed after infection, but from the lung samples of large rat and pig guinea, the genomic RNA of SARS-CoV could be detected by RT-PCR at day 14 post infection, this suggested that SARS-CoV could replicate in these animals. After inoculated with SARS-CoV, all inoculated cynomolgus and rhesus macaques had developed interstitial pneumonia of differing severity. These changes on histopathology were similar to that seen in SARS patients, but the pathological lesions were less severe than that of human. Except interstitial pneumonia, no other characterized pathological changes were observed. This suggested cynomolgus and rhesus macaques were not the ideal animal model for SARS in fact, but they could serve as animal model for SARS when a more ideal animal model is absent.


Subject(s)
Disease Models, Animal , Severe Acute Respiratory Syndrome/virology , Animals , Chickens , Humans , Macaca fascicularis , Macaca mulatta , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Severe Acute Respiratory Syndrome/pathology , Virus Replication
10.
Zhonghua Bing Li Xue Za Zhi ; 32(3): 209-11, 2003 Jun.
Article in Chinese | MEDLINE | ID: mdl-12882683

ABSTRACT

OBJECTIVE: Electron microscopical study of infected cells to identify the pathogenic agent of SARS. METHODS: Vero E6 cells infected with lung autopsy samples or nasopharyngeal swabs from SARS patients of Beijing and Guangzhou were inoculated. The supernatant and cultured cells exhibiting identifiable cytopathic effect (CPE) were prepared for electron microscopic study. RESULTS: Examination of CPE cells on thin-section revealed characteristic coronavirus particles within the cisternae of endoplasmic reticulum, Golgi apparatus, vesicles and extracellular space. They were mainly spherical or oval in shape, annular or dense, about 80 nm in diameter. Negative-stain electron microscopy identified coronavirus particles in culture supernatant, 80 - 120 nm in diameter, with club-shaped surface projections. Elongated, rod-, kidney- or other irregular shaped virons with the size of 100 - 200 nm by 60 - 90 nm were also found in the cultured cells infected with the lung samples from the Guangdong patients. Infectious virons entered cells by endocytosis or membrane fusion and released through a budding process. CONCLUSION: These data indicate a novel coronavirus as the causative agent of SARS. Most viral particles showed typical characteristics of coronavirus. The potential role of special shape viruses is expected to be further investigated.


Subject(s)
Severe Acute Respiratory Syndrome/virology , Severe acute respiratory syndrome-related coronavirus/ultrastructure , Animals , Chlorocebus aethiops , Humans , Microscopy, Electron , Vero Cells
11.
Chin Sci Bull ; 48(10): 941-948, 2003.
Article in English | MEDLINE | ID: mdl-32214698

ABSTRACT

The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS-associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymous mutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to be involved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the M protein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides no evidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of other possible SARS-related pathogen(s).

12.
Genomics Proteomics Bioinformatics ; 1(2): 101-7, 2003 May.
Article in English | MEDLINE | ID: mdl-15626340

ABSTRACT

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.


Subject(s)
Genetic Variation , Genome, Viral , Phylogeny , Severe Acute Respiratory Syndrome/genetics , Severe acute respiratory syndrome-related coronavirus/genetics , Base Sequence , China , Cluster Analysis , Gene Components , Genotype , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA
13.
Genomics Proteomics Bioinformatics ; 1(3): 180-92, 2003 Aug.
Article in English | MEDLINE | ID: mdl-15629030

ABSTRACT

Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city's hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.


Subject(s)
Genome, Viral , Severe acute respiratory syndrome-related coronavirus/genetics , Haplotypes , Humans , Mutation , Open Reading Frames , Phylogeny
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