摘要
Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
Subject(s)
Humans , Glycosylation , Pancreatic Neoplasms/pathology , Adenocarcinoma , Proto-Oncogene Proteins p21(ras)/metabolism , Glycoproteins , Mass Spectrometry , Biomarkers/metabolism , Polysaccharides摘要
Long non-coding RNA(LncRNA)has attracted increasing attention over the recent years. It is closely related to the occurrence and development of human diseases based on numerous academic researches. Analysis of the biological function of LncRNA in depth may lead to great breakthroughs in clarifying pathogenesis of many diseases and provide possible targets for intervention. Recent studies have revealed the importance of LncRNA in the progression of heart failure(HF), the final stage of many cardiovascular diseases. This review summarized the new findings of LncRNA in prognosis and treatment of HF.
摘要
The nucleocapsid protein (N protein) has been found to be an antigenic protein in a number of coronaviruses. Whether the N protein in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is antigenic remains to be elucidated. Using Western blot and Enzyme-linked Immunosorbent Assay (ELISA), the recombinant N proteins and the synthesized peptides derived from the N protein were screened in sera from SARS patients. All patient sera in this study displayed strong positive immunoreactivities against the recombinant N proteins, whereas normal sera gave negative immunoresponses to these proteins, indicating that the N protein of SARS-CoV is an antigenic protein. Furthermore, the epitope sites in the N protein were determined by competition experiments, in which the recombinant proteins or the synthesized peptides competed against the SARS-CoV proteins to bind to the antibodies raised in SARS sera. One epitope site located at the C-terminus was confirmed as the most antigenic region in this protein. A detailed screening of peptide with ELISA demonstrated that the amino sequence from Codons 371 to 407 was the epitope site at the C-terminus of the N protein. Understanding of the epitope sites could be very significant for developing an effective diagnostic approach to SARS.
Subject(s)
Humans , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Epitopes , Chemistry , Allergy and Immunology , Nucleocapsid Proteins , Chemistry , Allergy and Immunology , Peptide Fragments , Plasmids , Recombinant Proteins , Allergy and Immunology , Metabolism , Severe acute respiratory syndrome-related coronavirus , Genetics , Allergy and Immunology , Metabolism摘要
AIM: To investigate the relations between the proliferation and phenotype change of adventitial cells and the expression of T GF-?1 in adventitia after arterial injury. METHODS: After abdominal artery injury in rabbits, adventitial cel l proliferation and phenotype were identified by immunohistochemistry, transmissi on electron microscope and in situ Hybridization. RESULTS: Three days and 7 days after injury, the PCNA-positive ce lls were significantly increased. The previously weakly actin-positive adventiti al cells became strong-actin staining, the typical myofibroblast featurses of ad ventitial cells were detected by TEM 7 and 14 days after injury. Three days afte r vascular injury, there was a marked increase in the nu mber of cells that demonstrated the presence of TGF-?1 transcripts within the adventitia. Seven days after arterial injury, adventitial cells continued to ex press TGF-?1. on day 28, the number of TGF-?1-expressing cells was markedly r e duced in the adventitia. CONCLUSION: This study demonstrates that the proliferation and p henotype modulation of adventitial cells are associated with induction of TGF- ?1 expression in adventitia after arterial injury.