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Biomedical subjects

Ying-Ying Xu

Publications and source records attributed to Ying-Ying Xu.

6 recordsLinked to original sources

Knowledge-enhanced protein subcellular localization prediction from 3D fluorescence microscope images.

MOTIVATION: Pinpointing the subcellular location of proteins is essential for studying protein function and related diseases. Advances in spatial proteomics have shown that automatic recognition of protein subcellular localization from images could highly facilitate protein translocation analysis and biomarker discovery, but existing machine-learning works have been mostly limited to processing 2D images. By contrast, 3D images have higher spatial resolution and allow researchers to observe cellular structures in their natural context, but currently, there are only a few studies of 3D image processing for protein distribution analysis due to the lack of data and complexity of modeling. RESULTS: We developed a knowledge-enhanced protein subcellular localization model, KE3DLoc, which could recognize distribution patterns in 3D fluorescence microscope images using deep learning methods. The model designs an image feature extraction module that incorporates information from 3D and 2D projected cells and implements asymmetric loss and confidence weights to address data imbalance and weak cell annotation issues. Besides, considering that the biological knowledge in the Gene Ontology (GO) database can provide valuable support for protein location understanding, the KE3DLoc model incorporates a novel knowledge enhancement module that optimizes the protein representation by related knowledge graphs derived from the GO. Since the image module and the knowledge module calculate features from different levels, KE3DLoc designs protein ID aggregation to enhance the consistency of protein features across different cells. Experimental results on three public datasets have demonstrated that the KE3DLoc significantly outperforms existing methods and provides valuable insights for spatial proteomics research. AVAILABILITY AND IMPLEMENTATION: All datasets and codes used in this study are available at GitHub: https://github.com/PRBioimages/KE3DLoc.

Microscopy, Fluorescence↗

Apoptosis induced by all-trans retinoic acid in N-acetylglucosaminyltransferase V repressed human hepatocarcinoma cells is mediated through endoplasmic reticulum stress.

We previously demonstrated that endoplasmic reticulum (ER) stress was triggered in human hepatocarcinoma 7721 cells transfected with antisense cDNA of N-acetylglucosaminyltransferase V (GnT-V-AS/7721) which were more susceptible to apoptosis induced by all-trans retinoic acid (ATRA). In the present study, we report that ATRA-induced apoptosis in GnT-V-AS/7721 cells is mediated through ER stress. We show here that ER stress is enhanced in GnT-V-AS/7721 cells with 80 microM ATRA treatment for 24 h, which is evidenced by the increase of GRP78/Bip, C/EBP-homologous protein-10 (CHOP, also known as GADD153) and spliced XBP1. Additionally, activation of caspase-12, caspase-9, and -3 was detected, and apoptosis morphology was observed in GnT-V-AS/7721 cells with ATRA treatment. These results suggest that ATRA enhances the ER stress triggered in GnT-V-AS/7721 cells, which represents a novel mechanism of ATRA to induce apoptosis. We further observed that GnT-V was significantly repressed and the structure of N-glycans was changed in GnT-V-AS/7721 cells with 80 microM ATRA treatment for 24 h, suggesting that repression of GnT-V by ATRA causes the enhanced ER stress and ER stress-mediated apoptosis in GnT-V-AS/7721 cells.

Apoptosis↗

Induction of apoptosis in SGC-7901 cells by polysaccharide-peptide GFPS1b from the cultured mycelia of Grifola frondosa GF9801.

The biological function of GFPPS1b, a novel polysaccharide-peptide isolated from cultured mycelia of Grifola frondosa GF9801, was well investigated. GFPS1b has anti-tumor activity and can significantly inhibit the proliferation of SGC-7901 cells, whereas slightly influences the growth of human normal liver cell line L-02. When treated with GFPS1b, SGC-7901 cells showed typical apoptotic morphological features such as the loss of villus and appearance of apoptotic bodies on the cell surface, volume reduction, and chromatin condensation, by scanning electron microscopy (SEM) and fluorescent microscopy (Hoechst 33342). The results of flow cytometry analysis and annexin V-PI assay showed that the SGC-7901 cell cycle was arrested in the G(2)/M phase, the subdiploid peak of DNA characteristic of apoptotic was also observed, and the apoptosis ratio was about 15.08%. DNA isolated from SGC-7901 cells cultured with GFPS1b showed a typical DNA 'ladders' of apoptosis in agarose gel electrophoresis. Further investigation results showed that the apoptotic machinery of SGC-7901 induced by GFPS1b was associated with drop in mitochondrial trans-membrane potential, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3. Our finding suggests that GFPS1b could suppress SGC-7901 cell growth and reduce cell survival via arresting cell cycle and inducing apoptosis of tumor cells.

Antineoplastic Agents, Phytogenic↗

1-Deoxymannojirimycin, the alpha1,2-mannosidase inhibitor, induced cellular endoplasmic reticulum stress in human hepatocarcinoma cell 7721.

Alpha1,2-mannosidases, key enzymes in N-glycan processing and located both in the endoplasmic reticulum and golgi, have been targets in the development of anti-cancer therapies. Previous studies have shown its involvement in protein degradation. In this study, 1-deoxymannojirimycin, a specific inhibitor of alpha1,2-mannosidase and generating 'high mannose' type of N-glycan, was treated in human hepatocarcinoma 7721 cells and induced the endoplasmic reticulum stress. Key moleculars as XBP1 and GRP78/Bip were activated and up-regulated, which suggested the UPR pathway was activated. The cleavage of caspase-12, -9, and -3 was also detected, which implicated the ER stress was triggered and apoptosis occurred in H7721 cells. The results indicate the 'high Man' structure generated by 1-deoxymannojirimycin may constitute potential novel mechanism for ER stress and caspase-12 pathway of cell apoptosis.

1-Deoxynojirimycin↗

[Analysis of 60 masses in the nasal vestibule].

OBJECTIVE: To summarize the treatment strategy of nasal vestibule masses. METHODS: Between May, 1982 and April,2003,60 patients with nasal vestibule mass were treated in our department. The clinical features of these masses were retrospectively analysed. RESULTS: Among 60 masses, 51 cases were benign tumors, 5 cases were inflammatory masses, and 4 cases were malignant tumors. All patients were surgically treated and discharged with complete recovery. Among patients with benign tumor and non-specific inflammatory mass, 37 patients with a median follow-up of 97 months without recurrence and malignant change. One patient with hidradenoma and one patient with rhinoscleroma recurred and another surgery was carried out. There was no recurrence after second surgery. 6 patients died of other diseases, and 11 patients lost follow-up. Two patients with malignant melanoma recurred after first surgery. Then the tumor was removed via lateral rhinotomy and died of local recurrence and liver metastasis. Two patients (one with papilloma carcinomatous change and another with non-Hodgkin lymphoma) were free of diseases 17 years or 5 years and 2 months respectively. CONCLUSIONS: Masses of different histological types can be found in the nasal vestibule. Surgical removal is the treatment of choice. The approaches are determined on the basis of site, size and kind of the masses.

Adolescent↗

[Optimization of cDNA microarray fabrication].

To optimize and screen the most suitable target gene length,concentration and printing solution in cDNA microarray, housekeeping genes, such as beta actin and GAPDH, were selected as targets and hepatitis B virus gene as negative control. The RT-PCR primers that spanned at least one intron and whose products were at between 189 bp and 1078 bp were designed with primer premier 5.0, so did the hepatitis B virus gene PCR primer. After polymerase chain reaction, the products were purified with ethanol and dissolved in 3xSSC, 50% DMSO and 0.5 mol/L carbonate buffer(pH=9.0)respectively. The concentrations of target genes were adjusted at 0.5 microg/microL, 1.0 microg/microL and 1.5 microg/microL. The hybridization signals had a good specificity. No signal showed in either negative control (HBV) or blank control (printing solution only). There was no significant difference in target gene lengths. The P value of beta actin (189 bp,491 bp,974 bp) and GAPDH (227 bp,552 bp,1078 bp) was 0.378 and 0.866 respectively. There was no significant difference among concentrations(P=0.648),too. However, the higher the concentration was, the stronger the signals would be. Among the three kinds of printing solution, 50% DMSO was the best (P=0.0001), while the other two had no difference by multi-comparison (P=0.142). The target gene at length between 200 bp and 1000 bp has got the same hybridization signals.50% DMSO printing solution and the target gene concentration of 0.5 microg/microl are suitable for good hybridization.

English Abstract↗