Expression patterns of AEG-1 in the normal brain.

Astrocyte elevated gene-1 (AEG-1) is a well-known oncogene implicated in various types of human cancers, including brain tumors. Recently, AEG-1 has also been reported to play pivotal roles in glioma-associated neurodegeneration and neurodegenerative diseases like Parkinson's disease and amyotrophic lateral sclerosis. However, the normal physiological functions and expression patterns of AEG-1 in the brain are not well understood. In this study, we investigated the expression patterns of AEG-1 in the normal mouse brain and found that AEG-1 is widely expressed in neurons and neuronal precursor cells, but little in glial cells. We observed differential expression levels of AEG-1 in various brain regions, and its expression was mainly localized in the cell body of neurons rather than the nucleus. Additionally, AEG-1 was expressed in the cytoplasm of Purkinje cells in both the mouse and human cerebellum, suggesting its potential role in this brain region. These findings suggest that AEG-1 may have important functions in normal brain physiology and warrant further investigation. Our results may also shed light on the differential expression patterns of AEG-1 in normal and pathological brains, providing insights into its roles in various neurological disorders.

A derivative of epigallocatechin-3-gallate induces apoptosis via SHP-1-mediated suppression of BCR-ABL and STAT3 signalling in chronic myelogenous leukaemia.

BACKGROUND AND PURPOSE: Epigallocatechin-3-gallate (EGCG) is a component of green tea known to have chemo-preventative effects on several cancers. However, EGCG has limited clinical application, which necessitates the development of a more effective EGCG prodrug as an anticancer agent. EXPERIMENTAL APPROACH: Derivatives of EGCG were evaluated for their stability and anti-tumour activity in human chronic myeloid leukaemia (CML) K562 and KBM5 cells. KEY RESULTS: EGCG-mono-palmitate (EGCG-MP) showed most prolonged stability compared with other EGCG derivatives. EGCG-MP exerted greater cytotoxicity and apoptosis in K562 and KBM5 cells than the other EGCG derivatives. EGCG-MP induced Src-homology 2 domain-containing tyrosine phosphatase 1 (SHP-1) leading decreased oncogenic protein BCR-ABL and STAT3 phosphorylation in CML cells, compared with treatment with EGCG. Furthermore, EGCG-MP reduced phosphorylation of STAT3 and survival genes in K562 cells, compared with EGCG. Conversely, depletion of SHP-1 or application of the tyrosine phosphatase inhibitor pervanadate blocked the ability of EGCG-MP to suppress phosphorylation of BCR-ABL and STAT3, and the expression of survival genes downstream of STAT3. In addition, EGCG-MP treatment more effectively suppressed tumour growth in BALB/c athymic nude mice compared with untreated controls or EGCG treatment. Immunohistochemistry revealed increased caspase 3 and SHP-1 activity and decreased phosphorylation of BCR-ABL in the EGCG-MP-treated group relative to that in the EGCG-treated group. CONCLUSIONS AND IMPLICATIONS: EGCG-MP induced SHP-1-mediated inhibition of BCR-ABL and STAT3 signalling in vitro and in vivo more effectively than EGCG. This derivative may be a potent chemotherapeutic agent for CML treatment.

Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells.

BACKGROUND: Osteopontin (OPN) is one of important molecular targets in cancer progression, metastasis as a calcium-binding, extracellular-matrix-associated protein of the small integrin-binding ligand and, N-linked glycoprotein. In the present study, anti-metastatic mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated on OPN enhanced metastasis in NCI-H460 non- small cell lung cancer cells. METHODS: Cell viability was measured by MTT assay. Adhesion and invasion assays were carried out to see that EEOS inhibited cell adhesion and invasion in OPN treated and non-treated NCI-H 460 cells. RT-PCR was used to determine the mRNA levels of uPA, uPAR, and EGFR. RESULTS: EEOS significantly inhibited cell adhesion and invasion in OPN treated and non treated NCI-H460 cells, though EEOS did not show any toxicity up to 200 µg/ml. EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated the expression of CD44 in NCI-H460 cells. In addition, EEOS effectively suppressed the expression of phosphatidylinositide 3-kinases (PI3K) and cyclooxygenase 2 (COX-2) and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells. Also, EEOS significantly attenuated the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and epidermal growth factor receptor (EGFR) at mRNA level and reduced vascular endothelial growth factor (VEGF) production and MMP-9 activity in OPN treated NCI-H460 cells. Furthermore, PI3K/Akt inhibitor LY294002 enhanced anti-metastatic potential of EEOS to attenuate the expression of uPA and MMP-9 in OPN treated NCI-H 460 cells. CONCLUSION: Overall, our findings suggest that anti-metastatic mechanism of EEOS is mediated by inhibition of PI3K/Akt in OPN treated NCI-H460 non-small cell lung cancer cells.

Bioimaging of targeting cancers using aptamer-conjugated carbon nanodots.

Using the excellent emission properties of carbon nanodots, we have developed an aptamer-conjugated imaging probe for targeting cancers.

Carbon nanodot-based self-delivering microRNA sensor to visualize microRNA124a expression during neurogenesis.

MicroRNAs (miRNAs, miRs) are recognized as regulators of gene expression related to cellular development and diseases. In this study, we developed a carbon nanodot (C-dot)-based miR124a molecular beacon (miR124a CMB). The C-dots were purified from candle soot (cC-dots) by thermal oxidation. The double-stranded DNA oligonucleotide containing a miR124a binding site and black hole quencher 1 (miR124a sensing oligo) was further conjugated with the cC-dots to form the miR124a CMB. P19 cells were incubated with the miR124a CMB to sense miR124a expression during neurogenesis. The physical properties of the cC-dots showed multi-color light emission with various excitation wavelengths, a broad size distribution ranging from 2 to 4 nm, a graphitic carbon core (sp2), an abundance of carboxyl groups on the surface, no evidence of cellular toxicity and a high level of self-promoted uptake into cells. The miR124a CMB showed great fluorescence quenching in the absence of miR124a. The miR124a CMB internalized into P19 cells successfully visualized a gradual increase in miR124a expression during neuronal differentiation by providing signal-on imaging activity acquired by the following mechanism: the miR124a, which was highly expressed during neurogenesis, was bound to the miR124a binding site, resulting in the detachment of the quencher from the miR124a CMB and producing fluorescence recovery. The miR124a CMB demonstrated great specificity for sensing miR124a biogenesis with the advantages of self-passivated carboxyl groups, no toxicity, and self-illumination and highly self-promoted cellular uptake which will make the sensing of other various miRNAs related to diseases easy, convenient and accurate.