MOESM1 of Chiral polymer modified nanoparticles selectively induce autophagy of cancer cells for tumor ablation

Additional file 1: Figure S1. Stability in different solutions as indicated of l-PAV-AuNPs and d-PAV-AuNPs. (a) Photos and (b) UV–Vis-NIR of l-PAV-AuNPs or d-PAV-AuNPs in different solutions including saline, PBS, cell medium, fetal bovine serum and dilution of whole blood of the mice for 3 days. Figure S2. The toxicity study of l/d-PAV-AuNPs. (a) Dose- and chirality-dependent cytotoxicity of l/d-PAV-AuNPs in MDA-MB-231 cells, 3T3 fibroblasts and HBL-100 cells respectively. (b) Apoptosis rates of the MDA-MB-231 cells, 3T3 fibroblasts and HBL-100 cells treated with PAV-AuNPs, respectively. FCM analysis was tested via Annexin V-FITC and PI as probes. (c) Expression levels of LC3 in MDA-MB-231 cells, 3T3 fibroblasts and HBL-100 cells with PAV-AuNPs treatment, separately. GAPDH was used as a loading control. Figure S3. Biodistribution of PAV-AuNPs in vivo. The in vivo biodistribution of PAV-AuNPs was analyzed by testing the Au content in main organs (liver, kidneys, spleen, heart, and lung) of mice at 1 and 30 days post intravenous injection, separately. * and ** present p < 0.05 and p < 0.01, respectively

DataSheet_1_Investigating the role of FADS family members in breast cancer based on bioinformatic analysis and experimental validation.docx

Breast cancer (BC) is the most common malignant tumor in women worldwide. Emerging evidence indicates the significance of fatty acid metabolism in BC. Fatty acid desaturase (FADS) is closely associated with cancer occurrence and development. Here, bioinformatic analysis and experimental validation were applied to investigate the potential functions of FADS in BC. Several public databases, including TCGA, GEO, HPA, Kaplan–Meier plotter, STRING, DAVID, cBioPortal, TIMER, TRRUST, and LinkedOmics were used to determine mRNA/protein expression levels, prognostic significance, functional enrichment, genetic alterations, association with tumor-infiltrating immune cells, and related transcription factors and kinases. BC tissues showed higher and lower mRNA expression of FADS2/6/8 and FADS3/4/5, respectively. FADS1/2/6 and FADS3/4/5 showed higher and lower protein expression levels, respectively, in BC tissues. Moreover, FADS1/7 up- and FADS3/8 down-regulation predicted poor overall and recurrence-free survival, while FADS2/5 up- and FADS4 down-regulation were associated with poor recurrence-free survival. Receiver operating characteristic curves revealed that FADS2/3/4/8 were indicative diagnostic markers. FADS family members showing differential expression levels were associated with various clinical subtypes, clinical stages, lymph node metastasis status, copy number variants, DNA methylation, and miRNA regulation in BC. The mRNA expression level of FADS1/2/3/4/5/7/8 was observed to be significantly negatively correlated with DNA methylation. FADS1/2 upregulation was significantly correlated with clinical stages. FADS1/4 expression was obviously lower in BC patients with higher lymph node metastasis than lower lymph node metastasis, while FADS7/8 expression was obviously higher in BC patients with higher lymph node metastasis than lower lymph node metastasis. FADS family members showed varying degrees of genetic alterations, and Gene Ontology and KEGG pathway enrichment analyses suggested their involvement in lipid metabolism. Their expression level was correlated with immune cell infiltration levels. FADS2 was chosen for further validation analyses. We found FADS2 to be significantly over-expressed in clinical BC tissue samples. The proliferation, migration, and invasion abilities of MDA-MB-231 and BT474 cells were significantly reduced after FADS2 knockdown. Furthermore, FADS2 may promote the occurrence and development of BC cells via regulating the epithelial–mesenchymal transition (EMT) pathway. Altogether, our results suggest that FADS1/2/3/4 can serve as potential therapeutic targets, prognostic indicators, and diagnostic markers in patients with BC.</p

Overcoming Clopidogrel Resistance: Discovery of Vicagrel as a Highly Potent and Orally Bioavailable Antiplatelet Agent

A series of optically active 2-hydroxytetrahydrothienopyridine derivatives were designed and synthesized as prodrugs of clopidogrel thiolactone in order to overcome clopidogrel resistance. The final compounds were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. Compound <b>9a</b> was selected for further in vitro and in vivo metabolism studies, since its potency was comparable to that of prasugrel and was much higher than that of clopidogrel. Preliminary pharmacokinetic study results showed that the bioavailability of clopidogrel thiolactone generated from <b>9a</b> was 6-fold higher than that generated from clopidogrel, implying a much lower clinically effective dose for <b>9a</b> in comparison with clopidogrel. In summary, <b>9a</b> (vicagrel) holds great promise as a more potent and a safer antiplatelet agent that might have the following advantages over clopidogrel: (1) no drug resistance for CYP2C19 poor metabolizers; (2) lower dose-related toxicity due to a much lower effective dose; (3) faster onset of action

Quantitative Glycome Analysis of N‑Glycan Patterns in Bladder Cancer vs Normal Bladder Cells Using an Integrated Strategy

Diagnosis of bladder cancer, one of the most common types of human cancer, at an early (nonmuscle-invasive) stage is the best way to reduce the mortality rate. Tumor malignancy in general is closely associated with alterations of glycan expression. Glycosylation status, particularly global glycomes, in bladder cancer has not been well studied. We integrated lectin microarray and mass spectrometry (MS) methods to quantitatively analyze and compare glycan expression in four bladder cancer cell lines (KK47, YTS1, J82, T24) and one normal bladder mucosa cell line (HCV29). Glycopattern alterations were analyzed using lectin microarray analysis and confirmed by lectin staining and lectin blotting. Associations of glycopatterns with diverging stages were evaluated by lectin histochemistry on tissue microarrays. N-Glycans were derivatized by amidation of sialylated glycans with acetohydrazide and reductive amination with the stable isotope tags [¹²C₆]- and [¹³C₆]-aniline, and were quantitatively analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). N-Glycan biosynthesis-associated proteins were quantitatively analyzed by a stable isotope labeling by amino acids in cell culture (SILAC) proteomics method, which revealed significant differences in expression of 13 glycosyltransferases and 4 glycosidases. Our findings indicate that sialyl Lewis X (sLe^x), terminal GalNAc and Gal, and high mannose-type N-glycans were more highly expressed in bladder cancer cells and tissues than in normal cells. Bladder cancer cells showed high expression of core-fucosylated N-glycans but low expression of terminally fucosylated N-glycans. Each of these glycome changes may be directly related to bladder cancer progression