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  • 1
    In: Journal of Hepatology, Elsevier BV, Vol. 72, No. 4 ( 2020-04), p. 761-773
    Type of Medium: Online Resource
    ISSN: 0168-8278
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2027112-8
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  • 2
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 11 ( 2021-1-18)
    Abstract: Influenza A viruses, especially H3N2 and H1N1 subtypes, are viruses that often spread among humans and cause influenza pandemic. There have been several big influenza pandemics that have caused millions of human deaths in history, and the threat of influenza viruses to public health is still serious nowadays due to the frequent antigenic drift and antigenic shift events. However, only few effective anti-flu drugs have been developed to date. The high development cost, long research and development time, and drug side effects are the major bottlenecks, which could be relieved by drug repositioning. In this study, we proposed a novel antiviral Drug Repositioning method based on minimizing Matrix Nuclear Norm (DRMNN). Specifically, a virus-drug correlation database consisting of 34 viruses and 205 antiviral drugs was first curated from public databases and published literature. Together with drug similarity on chemical structure and virus sequence similarity, we formulated the drug repositioning problem as a low-rank matrix completion problem, which was solved by minimizing the nuclear norm of a matrix with a few regularization terms. DRMNN was compared with three recent association prediction algorithms. The AUC of DRMNN in the global fivefold cross-validation (fivefold CV) is 0.8661, and the AUC in the local leave-one-out cross-validation (LOOCV) is 0.6929. Experiments have shown that DRMNN is better than other algorithms in predicting which drugs are effective against influenza A virus. With H3N2 as an example, 10 drugs most likely to be effective against H3N2 viruses were listed, among which six drugs were reported, in other literature, to have some effect on the viruses. The protein docking experiments between the chemical structure of the prioritized drugs and viral hemagglutinin protein also provided evidence for the potential of the predicted drugs for the treatment of influenza.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564217-0
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Paediatrics & Child Health Vol. 26, No. 1 ( 2021-02-01), p. e6-e10
    In: Paediatrics & Child Health, Oxford University Press (OUP), Vol. 26, No. 1 ( 2021-02-01), p. e6-e10
    Abstract: To characterize and compare children with correct diagnosis (CD) and misdiagnosis (MD) of tracheobronchial foreign body (TBFB). Methods A retrospective study was performed to review the medical records of children with CD group and MD group of TBFB. CD was defined when TBFB was identified during the first hospital visit. Otherwise, MD was considered. Demographic information, including gender, age, and clinical information, including clinical presentations and characteristics of foreign bodies, were retrieved. These characteristics were compared between two groups by Student’s t-test or Wilcoxon two-sample test, or Chi-square analysis or Fisher’s exact test, when appropriate. Results A total of 462 children with final diagnosis of TBFB were identified, with 276 children having CD and 186 children having MD. The most common location to identify the TBFB was right main bronchus in both CD and MD groups. Children with the previous history of respiratory tract foreign body were more likely to receive the CD. Children in MD group were more likely to have fever, as well as wheezing and crackles during physical examination. They were more likely to have pneumonia. Most common TBFB were peanuts. The majority of the TBFB were removed by the flexible bronchoscope coupled with forceps. Conclusion Careful history taking and physical examination, especially for those children with unclear causes for their pneumonia or asthma, or children with no improvement on the treatments, should be performed to rule out the possibility of TBFB. Bronchoscopy should be performed if necessary.
    Type of Medium: Online Resource
    ISSN: 1205-7088 , 1918-1485
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2174400-2
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  • 4
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 8, No. 4 ( 2017-04-06), p. e2736-e2736
    Abstract: Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. AJAP1 overexpression inhibited HCC progression and metastasis, while its silencing had the opposite effect both in vitro and in vivo . Furthermore, AJAP1 blocked epithelial–to–mesenchymal transition by interacting with β -catenin and inhibiting its nuclear translocation, which suppressed zinc finger E-box binding homeobox 1 (ZEB1) transcription. These results indicate that AJAP1 inhibits HCC metastasis, and is thus a potential therapeutic target for HCC treatment.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2541626-1
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  • 5
    In: Oncogene, Springer Science and Business Media LLC, Vol. 38, No. 3 ( 2019-1), p. 406-420
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2008404-3
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  • 6
    In: BMC Pulmonary Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: Kartagener syndrome is a subtype of primary ciliary dyskinesia that may exhibit various symptoms including neonatal respiratory distress and frequent infections of the lung, sinus and middle ear because of the impaired function of motile cilia. In addition to typical symptoms of primary ciliary dyskinesia, patients with Kartagener syndrome also show situs inversus. It is an autosomal recessive disorder which is mostly caused by mutations in DNAH5 . Kartagener syndrome is often underdiagnosed due to challenges in the diagnosis process. As next-generation sequencing becomes widely used in clinical laboratories, genetic testing provides an accurate approach to the diagnosis of Kartagener syndrome. Case presentation A 7-year-old female patient presented with runny nose of 6 years duration and recurrent cough with phlegm of 2 years duration. Kartagener syndrome was diagnosed through diagnostic tests such as nasal nitric oxide (NO) concentration and transmission electron microscopy, and after performing other exams that corroborated the diagnosis, such as computed tomography, bronchoscopy and hearing test. Whole-exome sequencing was performed for the patient and both parents. The pediatric patient was diagnosed as Kartagener syndrome with the typical symptoms of ciliary dyskinesia including bronchiectasis, sinusitis, conductive hearing loss and situs inversus along with a reduced nasal NO concentration and ciliary abnormalities. The patient carried two novel compound heterozygous mutations in DNAH5 , NM_001369:c.12813G  〉  A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term). Both mutations lead to premature stop codons and thus are pathogenic. The p. Trp4271Term and p. Leu3122Term mutations were inherited from the father and the mother of the patient individually. A literature review was also conducted to summarize DNAH5 mutations in pediatric patients with Kartagener syndrome across different ethnic groups. Conclusions Our study provides a good example of the diagnosis of Kartagener syndrome in pediatric patients using a series of diagnostic tests combined with genetic testing. Two novel loss-of-function mutations in DNAH5 were identified and validated in a pediatric patient with Kartagener syndrome.
    Type of Medium: Online Resource
    ISSN: 1471-2466
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2059871-3
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  • 7
    In: Molecular Cancer, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2019-12)
    Abstract: Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This study aims to explore molecular mechanisms underlying how ASPH network regulates designated exosomes to program development and progression of breast cancer. Methods Stable cell lines overexpressing or knocking-out of ASPH were established using lentivirus transfection or CRISPR-CAS9 systems. Western blot, MTT, immunofluorescence, luciferase reporter, co-immunoprecipitation, 2D/3-D invasion, tube formation, mammosphere formation, immunohistochemistry and newly developed in vitro metastasis were applied. Results Through physical interactions with Notch receptors, ligands (JAGs) and regulators (ADAM10/17), ASPH activates Notch cascade to provide raw materials (especially MMPs/ADAMs) for synthesis/release of pro-metastatic exosomes. Exosomes orchestrate EMT, 2-D/3-D invasion, stemness, angiogenesis, and premetastatic niche formation. Small molecule inhibitors (SMIs) of ASPH’s β-hydroxylase specifically/efficiently abrogated in vitro metastasis, which mimics basement membrane invasion at primary site, intravasation/extravasation (transendothelial migration), and colonization/outgrowth at distant sites. Multiple organ-metastases in orthotopic and tail vein injection murine models were substantially blocked by a specific SMI. ASPH is silenced in normal adult breast, upregulated from in situ malignancies to highly expressed in invasive/advanced ductal carcinoma. Moderate-high expression of ASPH confers more aggressive molecular subtypes (TNBC or Her2 amplified), early recurrence/progression and devastating outcome (reduced overall/disease-free survival) of breast cancer. Expression profiling of Notch signaling components positively correlates with ASPH expression in breast cancer patients, confirming that ASPH-Notch axis acts functionally in breast tumorigenesis. Conclusions ASPH-Notch axis guides particularly selective exosomes to potentiate multifaceted metastasis. ASPH’s pro-oncogenic/pro-metastatic properties are essential for breast cancer development/progression, revealing a potential target for therapy.
    Type of Medium: Online Resource
    ISSN: 1476-4598
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2091373-4
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  • 8
    In: Clinical and Translational Medicine, Wiley, Vol. 13, No. 9 ( 2023-09)
    Abstract: Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related deaths worldwide. Therapeutic options for advanced HCC are limited, which is due to a lack of full understanding of pathogenesis. Cellular senescence is a state of cell cycle arrest, which plays important roles in the pathogenesis of HCC. Mechanisms underlying hepatocellular senescence are not fully understood. LncRNA NEAT1 acts as an oncogene and contributes to the development of HCC. Whether NEAT1 modulates hepatocellular senescence in HCC is unknown. Methods The role of NEAT1 and KIF11 in cellular senescence and tumor growth in HCC was assessed both in vitro and in vivo. RNA pulldown, mass spectrometry, Chromatin immunoprecipitation (ChIP), luciferase reporter assays, RNA FISH and immunofluorescence (IF) staining were used to explore the detailed molecular mechanism of NEAT1 and KIF11 in cellular senescence of HCC. Results We found that NEAT1 was upregulated in tumor tissues and hepatoma cells, which negatively correlated with a senescence biomarker CDKN2A encoding p16INK4a and p14ARF proteins. NEAT1 was reduced in senescent hepatoma cells induced by doxorubicin (DOXO) or serum starvation. Furthermore, NEAT1 deficiency caused senescence in cultured hepatoma cells, and protected against the progression of HCC in a mouse model. During senescence, NEAT1 translocated into cytosol and interacted with a motor protein KIF11, resulting in KIF11 protein degradation and subsequent increased expression of CDKN2A in cultured hepatoma cells. Furthermore, KIF11 knockdown caused senescence in cultured hepatoma cells. Genetic deletion of Kif11 in hepatocytes inhibited the development of HCC in a mouse model. Conclusions Conclusively, NEAT1 overexpression reduces senescence and promotes tumor progression in HCC tissues and hepatoma cells, whereas NEAT1 deficiency causes senescence and inhibits tumor progression in HCC. This is associated with KIF11‐dependent repression of CDKN2A. These findings lay the foundation to develop potential therapies for HCC by inhibiting NEAT1 and KIF11 or inducing senescence.
    Type of Medium: Online Resource
    ISSN: 2001-1326 , 2001-1326
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2697013-2
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  • 9
    In: Oncogenesis, Springer Science and Business Media LLC, Vol. 9, No. 5 ( 2020-05-28)
    Abstract: Tumor cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect, but the involvement of Warburg effect in liver cancer cell metastasis is not well understood. In present study, our results indicate a positive correlation between glucose metabolism level and metastatic potential of hepatocellular carcinoma (HCC). We also observed that a long noncoding RNA-SOX2OT (lncRNA-SOX2OT) can not only increase the metastatic potential of HCC but also promote a pyruvate kinase M2 (PKM2)-mediated activation of glucose metabolism. Inhibition of PKM2 in HCC cells greatly compromises lncRNA-SOX2OT in promoting Warburg effect and metastasis. Furthermore, miR-122-5p was found being a direct target of lncRNA-SOX2OT in regulating PKM2 expression. Thus, our findings reveal that lncRNA-SOX2OT, a regulator of PKM2, could predispose HCC patients to metastases and may serve as a candidate for metastatic prediction and therapies in HCC patients.
    Type of Medium: Online Resource
    ISSN: 2157-9024
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2674437-5
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Pediatrics Vol. 11 ( 2023-2-22)
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 11 ( 2023-2-22)
    Abstract: An electronic literature search was performed using the keywords “tracheoesophageal fistula,” “endoscopic,” and “children” in the four major medical databases (Ovid, Embase, PubMed, and Web of Science) right from inception to September 2022. All English language articles describing the endoscopic interventional therapies of TEF in children were reviewed. Two independent researchers screened eligible articles at the title and abstract level. Full texts of potentially relevant articles were then screened again, and reference lists were screened manually to identify additional studies. Relevant data were extracted and analyzed. A synthesis of the relevant data was presented in descriptive form because of the heterogeneity of the included articles. The Chi-Squared test was used with a significance level of 5% ( P  & lt; 0.05). Results Among the 1,167 retrieved papers, a total of 46 studies describing 170 TEF patients with an age range of 0.3–175 months were included, including 11 cases of acquired tracheoesophageal fistula, 144 cases of recurrent tracheoesophageal fistula, and 15 cases of congenital tracheoesophageal fistula (H-type TEF). A total of 119 out of 170 fistulas were successfully blocked via endoscopic techniques with an overall success rate of 70.0%, while 48 fistulas failed to close by endoscopic interventions, following which the procedure was converted to open surgery. No obviously severe intraoperative/postoperative complications occurred during the follow-up period, but only a mild esophageal stricture was noticed in six patients and grade II tracheal stenosis in one patient. Two patients died from causes unrelated to endoscopic procedures, with a mortality rate of approximately 1.2%. A comparative assessment of different endoscopic interventional techniques for TEF that detected endotracheal stenting was performed in six patients and one fistula was successfully blocked (16.7%). De-epithelialization alone was performed in 65 patients and the fistula healed in 47 of them (72.3%), with the mean number of successful treatments required being 2.3 times. Chemical sealant injection was administered in 33 patients and success was achieved in 21 (63.6%). The average requirement for endoscopic procedures was 1.5 times. De-epithelialization, in combination with chemical sealant injection, was performed in 62 patients, achieving the highest success rate of 77.4% (48 patients). Other treatment methods were performed in four patients and successfully treatment outcomes were reported in two of them (50.0%). The mean number of successful treatments required was four times, and a treatment was converted to surgery in one patient (25.0%). An assessment of different TEF types showed that 9 out of 15 congenital TEFs, 7 out of 11 acquired TEFs, and 103 out of 144 recurrent TEFs were successfully occluded. A comparison of the success rate across multiple groups showed a significant difference with a score of P  & lt; 0.05, while there was no significant difference in the success rate of different TEF-type groups ( P  & gt; 0.05). Conclusion Endoscopic intervention is currently a preferred treatment modality for children with TEF because of its less-invasive nature, less complications, and high success rate. Among all interventional techniques, de-epithelialization, in combination with chemical sealant, has a higher success rate than other techniques. However, due to the limited number of cases reported for implementing many kinds of techniques, an ideal endoscopic interventional technique has yet to be devised, often necessitating more treatment applications and close follow-up.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2711999-3
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