The effects of micronisation on the characteristics and physicochemical properties of (a) an insoluble fibre-rich fraction (IFRF) prepared from orange peel and (b) cellulose were studied and compared. The results showed that micronisation techniques such as hall milling, jet milling and high-pressure micronisation could effectively (P < 0.05) reduce particle sizes to microscale, decrease the bulk density and improve the physicochemical properties (water-holding capacity, swelling capacity, oil-holding capacity, cation exchange capacity and glucose adsorption capacity) of IFRF and cellulose to different extents (up to 25-fold). After micronisation the inhibitory effects of these insoluble fibres towards alpha-amylase and pancreatic lipase were significantly increased (up to 5.8- and 7.8-fold respectively) and a redistribution of some fibre components from insoluble to soluble fractions was observed. It was concluded that these micronisation treatments, especially high-pressure micronisation, could effectively improve the functionalities of IFRF and cellulose, which might then be used as potential fibre-rich ingredients in functional food applications. (c) 2006 Society of Chemical Industry

G protein‐coupled estrogen receptor‐1 (GPER), a member of the G protein‐coupled receptor (GPCR) superfamily, mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non‐BCSCs of three patient‐derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER‐mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD‐Ser118 to sustain BCSC characteristics. Transfection with a dominant‐negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.

A novel nanocarrier for targeted delivery of anticancer drug doxorubicin (DOX) was fabricated with carbon dots (CDots) as the matrix. Fluorescent CDots capable of targeting folate receptor-positive cells first conjugate with boric acid and then couple with b-CD to produce the nanocarrier b-CD/CDots. DOX was encapsulated into the cavity of b-CD providing a maximum loading ratio of 27.3% at pH 7.4. Benefiting from pH-sensitive dissociation of DOX/b-CD inclusion complex and the cleavage of the bonding between boric acid and b-CD, pH-triggered release of drugs was realized, with an 82% release of the loaded drug at pH 5.0. Meanwhile, the fluorescence resonance energy trans-fer (FRET) occurs between CDots (donor) and DOX (acceptor), which may potentially facilitate monitoring/tracing of the drug delivery process. In vitro results further demonstrated the targeting capability of the nanocarrier towards folate receptor-positive cells. Moreover, confocal microscopy results, in accordance with that of flow cytometry analysis, confirmed the efficient intracellular uptake of DOX-b-CD/CDots and sustained release of DOX. This makes DOX-b-CD/CDots promising as biocompatible and multifunctional nanomedicine for targeted delivery, controlled release and real time monitoring/tracing of drugs.

Background and purpose: Abnormal mitochondrial metabolism has been described in the Alzheimer's disease (AD) brain. However, the relationship between AD pathophysiology and key mitochondrial processes remains elusive. The purpose of this study was to investigate whether mitochondrial complex I dysfunction is associated with amyloid aggrega-How to cite this article: Terada T, Therriault J, Kang MS, et al.Mitochondrial complex I abnormalities underlie neurodegeneration and cognitive decline in Alzheimer's disease.