METHODS: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification.
FINDINGS: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC
MATERIALS & METHODS: The fabricated core/shell nanofibers contained polycaprolactone/gelatin as the shell, and silk fibroin/VEGF as the core materials.
RESULTS: The results observed that the core/shell nanofibers interact to differentiate MSCs into smooth muscle cells by the expression of vascular smooth muscle cell (VSMC) contractile proteins α-actinin, myosin and F-actin.
CONCLUSION: The functionalized polycaprolactone/gelatin/silk fibroin/VEGF (250 ng) core/shell nanofibers were fabricated for the controlled release of VEGF in a persistent manner for the differentiation of MSCs into smooth muscle cells for vascular tissue engineering.
METHODS: We analysed the frequency, phenotype and functionality of peripheral blood MAIT cells, as well as γδ T cells, invariant natural killer T (iNKT) cells and natural killer (NK) cells with flow cytometry in a cross-sectional paediatric cohort (aged 2-15) consisting of 51 children with newly diagnosed type 1 diabetes, 27 autoantibody-positive (AAb+) at-risk children, and 113 healthy control children of similar age and HLA class II background. The frequency of MAIT cells was also assessed in a separate cross-sectional adult cohort (aged 19-39) of 33 adults with established type 1 diabetes and 37 healthy individuals of similar age.
RESULTS: Children with newly diagnosed type 1 diabetes displayed a proportional increase of CD8-CD27- MAIT cells compared with healthy control children (median 4.6% vs 3.1% of MAIT cells, respectively, p = 0.004), which was associated with reduced expression of C-C chemokine receptor (CCR)5 (median 90.0% vs 94.3% of MAIT cells, p = 0.02) and β7 integrin (median 73.5% vs 81.7% of MAIT cells, p = 0.004), as well as decreased production of IFN-γ (median 57.1% vs 69.3% of MAIT cells, p = 0.04) by the MAIT cells. The frequency of MAIT cells was also decreased in AAb+ children who later progressed to type 1 diabetes compared with healthy control children (median 0.44% vs 0.96% of CD3+ T cells, p = 0.04), as well as in adult patients with a short duration of type 1 diabetes (less than 6 years after diagnosis) compared with control individuals (median 0.87% vs 2.19% of CD3+ T cells, p = 0.007). No alterations in γδ T cell, iNKT cell or NK cell frequencies were observed in children with type 1 diabetes or in AAb+ children, with the exception of an increased frequency of IL-17A+ γδ T cells in children with newly diagnosed diabetes compared with healthy control children (median 1.58% vs 1.09% of γδ T cells, p = 0.002).
CONCLUSIONS/INTERPRETATION: Changes in the frequency and phenotype of circulating MAIT cells were detectable before, at the onset and after diagnosis of type 1 diabetes in cross-sectional cohorts. Our results suggest a possible temporal association between peripheral blood MAIT cell alterations and the clinical onset of type 1 diabetes. Graphical abstract.
Objective: This study aimed to determine the effects of selected phytoestrogens on annexin A1 (ANXA1) expression, mode of cell death and cell cycle arrest in different human leukemic cell lines.
Methods: Cells viability were examined by MTT assay and ANXA1 quantification via Enzyme-linked Immunosorbent Assay. Cell cycle and apoptosis were examined by flow cytometer and phagocytosis effect was evaluated using haematoxylin-eosin staining.
Results: Coumestrol significantly (p