The mechanism of collagen secretion is not completely understood. It is found that cTAGE5 binds to TANGO1, and it is suggested that collagen VII export from the ER is driven by a cTAGE5/TANGO1 complex.

Metabolized by liver sinusoidal endothelial cells, autotaxin (ATX) is a secreted enzyme considered to be associated with liver damage. We sought to clarify the diagnostic ability of ATX for liver fibrosis in 593 biopsy-confirmed hepatitis C virus (HCV)-infected patients. The diagnostic accuracy of ATX was compared with clinical parameters and the established fibrosis biomarkers Wisteria floribunda agglutinin-positive Mac-2-binding protein, FIB-4 index, AST-to-platelet ratio, and Forn’s index. Median ATX levels were consistently higher in female controls and patients than in their male counterparts (P < 0.01). Serum ATX concentration increased significantly according to liver fibrosis stage in overall and both genders (P < 0.001). The cutoff values of ATX for prediction of fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.8, 1.1, 1.3, and 1.7 mg/L, respectively, in male patients and 0.9, 1.7, 1.8, and 2.0 mg/L, respectively, in female patients. The area under the receiver operating characteristic curve for ATX to diagnose fibrosis of ≥F2 (0.861) in male patients was superior to those of FIB-4 index and Forn’s index (P < 0.001), while that in female patients (0.801) was comparable with those of the other markers. ATX therefore represents a novel non-invasive biomarker for liver fibrosis in HCV-infected patients.

Described herein is the enantioselective synthesis of multisubstituted biaryl derivatives by chiral phosphoric acid catalyzed asymmetric bromination. Two asymmetric reactions (desymmetrization and kinetic resolution) proceeded successively to afford chiral biaryls in excellent enantioselectivities (up to 99% ee). Both experimental and computational studies suggested that this excellent selectivity could be achieved via a highly organized hydrogen bond network among a substrate, a catalyst (chiral phosphoric acid), and a brominating reagent (N-bromophthalimide).

Gold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN). In this study, polyethylene-glycolylated AuNPs (P-AuNPs) were conjugated with Arg–Gly–Asp (RGD) peptides (RGD/P-AuNPs) to target cancer cells expressing RGD-binding integrins such as α5- and αv-integrins. RGD/P-AuNPs were internalized more efficiently and colocalized with integrins in the late endosomes and lysosomes of MDA-MB-231 cells. A combination of RGD/P-AuNPs and radiation reduced cancer cell viability and increased DNA damage compared to radiation alone in MDA-MB-231 cells. Moreover, the invasive activity of breast cancer cell lines after radiation treatment was significantly inhibited in the presence of RGD/P-AuNPs. Microarray analyses revealed that the expression of FN in irradiated cells was suppressed by combined use of RGD/P-AuNPs. Reduction of FN and downstream signaling may be involved in suppressing radiation-induced invasive activity by RGD/P-AuNPs. Our study suggests that RGD/P-AuNPs can target integrin-overexpressing cancer cells to improve radiation therapy by suppressing invasive activity in addition to sensitization. Thus, these findings provide a possible clinical strategy for using AuNPs to treat invasive breast cancer following radiotherapy.

Phosphatidylserine (PS) has skewed distributions in the plasma membrane and is preferentially located in the inner leaflet of normal cells. Tumour cells, however, expose PS at the outer leaflet of cell surfaces, thereby potentially modulating the bio-signalling of cells. Interestingly, exosomes – or, more properly, small extracellular vesicles (sEVs) – which are secreted from tumour cells, are enriched with externalized PS, have been proposed as being involved in the progression of cancers, and could be used as a marker for tumour diagnostics. However, the sEV fractions prepared from various methods are composed of different subtypes of vesicles, and knowledge about the subtypes enriched with exposed PS is still limited. Here, we differentiated sEVs from cancer cell lines by density gradient centrifugation and characterized the separated fractions by using gold-labelling of PS in atomic force microscopy, thrombin generation assay, size and zeta potential measurements, and western blot analysis. These analyses revealed a previously unreported PS + -enriched sEV subtype, which is characterized by a lower density than that of canonical exosomes (1.06 g/ml vs. 1.08 g/ml), larger size (122 nm vs. 105 nm), more negative zeta potential (−28 mV vs. −21 mV), and lower abundance of canonical exosomal markers. The identification of the PS-exposed subtype of sEVs will provide deeper insight into the role of EVs in tumour biology and enhance the development of EV-based tumour diagnosis and therapy.