RPLP1 promotes tumor metastasis and is associated with a poor prognosis in triple-negative breast cancer patients.

BACKGROUND: Cancer metastasis is the major reason for cancer related deaths, and the mechanism of cancer metastasis still unclear. RPLP1, a member of a group of proteins known as ribosomal proteins, is associated with tumorigenesis and primary cell immortalization and is involved in cellular transformation. However, the expression and potential function of RPLP1 in TNBC remain unclear. METHODS: The expression of RPLP1 in TNBC tissues and cell lines were detected with Real-Time PCR and western blotting. 81 cases of TNBC tissue samples and adjacent non-tumor tissue samples were tested by immunochemistry to determine the correlation between the RPLP1 expression and clinicopathological characteristics. In vitro, we determined the role and mechanistic pathways of RPLP1 in tumor metastasis in TNBC cell lines. RESULTS: In this study, we detected high levels of RPLP1 expression in TNBC samples and cell lines. RPLP1 is upregulated in triple-negative breast cancer (TNBC) tissues and cells, and high expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, high RPLP1 expression was associated with a poor prognosis and was an independent prognostic marker for TNBC. In RPLP1-induced cancer metastasis, RPLP1 may increase cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition. CONCLUSIONS: Altogether, our findings indicate RPLP1 is a poor prognostic potential biomarker and anti-metastasis candidate therapeutic target in triple-negative breast cancer.

Computational screening for new neuroprotective ingredients against Alzheimer's disease from bilberry by cheminformatics approaches.

Bioactive ingredients from natural products have always been an important resource for the discovery of drugs for Alzheimer's disease (AD). Senile plaques, which are formed with amyloid-beta (Aß) peptides and excess metal ions, are found in AD brains and have been suggested to play an important role in AD pathogenesis. Here, we attempted to design an effective and smart screening method based on cheminformatics approaches to find new ingredients against AD from Vaccinium myrtillus (bilberry) and verified the bioactivity of expected ingredients through experiments. This method integrated advanced artificial intelligence models and target prediction methods to realize the stepwise analysis and filtering of all ingredients. Finally, we obtained the expected new compound malvidin-3-O-galactoside (Ma-3-gal-Cl). The in vitro experiments showed that Ma-3-gal-Cl could reduce the OH· generation and intracellular ROS from the Aß/Cu2+/AA mixture and maintain the mitochondrial membrane potential of SH-SY5Y cells. Molecular docking and Western blot results indicated that Ma-3-gal-Cl could reduce the amount of activated caspase-3 via binding with unactivated caspase-3 and reduce the expression of phosphorylated p38 via binding with mitogen-activated protein kinase kinases-6 (MKK6). Moreover, Ma-3-gal-Cl could inhibit the Aß aggregation via binding with Aß monomer and fibers. Thus, Ma-3-gal-Cl showed significant effects on protecting SH-SY5Y cells from Aß/Cu2+/AA induced damage via antioxidation effect and inhibition effect to the Aß aggregation.

DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway.

Oxidative stress in the brain is highly related to the pathogenesis of Alzheimer's disease (AD). It could be induced by the overproduction of reactive oxygen species (ROS), produced by the amyloid beta (Aß) peptide and excess copper (Cu) in senile plaques and cellular species, such as ascorbic acid (AA) and O2. In this study, the protective effect of 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone (DHPA) on Aß(1-42)/Cu2+/AA mixture-treated SH-SY5Y cells was investigated via in vitro and in silico studies. The results showed that DHPA could inhibit Aß/Cu2+/AA-induced SH-SY5Y apoptosis, OH· production, intracellular ROS accumulation, and malondialdehyde (MDA) production. Further research demonstrated that DHPA could decrease the ratio of Bax/Bcl-2 and repress the increase of mitochondrial membrane potential (MMP) of SH-SY5Y cells, to further suppress the activation of caspase-3, and inhibit cell apoptosis. Meanwhile, DHPA could inhibit the Aß/Cu2+/AA-induced phosphorylation of Erk1/2 and P38 in SH-SY5Y cells, and increase the expression of P-AKT. Furthermore, DHPA could bind to Keap1 to promote the separation of Nrf2 to Keap1 and activate the Keap1/Nrf2/HO-1 signaling pathway to increase the expression of heme oxygenase-1 (HO-1), quinone oxidoreductase-1 (NQO1), glutathione (GSH), and superoxide dismutase (SOD). Thus, our results demonstrated that DHPA could inhibit Aß/Cu2+/AA-induced SH-SY5Y apoptosis via scavenging OH·, inhibit mitochondria apoptosis, and activate the Keap1/Nrf2/HO-1 signaling pathway.

A label-free fluorescent peptide probe for sensitive and selective determination of copper and sulfide ions in aqueous systems.

A label free fluorescent peptide probe (HDSGWEVHH) was used for Cu2+ and S2- determination in aqueous solution. Our results demonstrated that HDSGWEVHH is highly selective and sensitive for monitoring free Cu2+ concentration via quenching of the probe fluorescence upon Cu2+ binding. The mechanism of the complexation is investigated with Cyclic Voltammetry (CV), 1H nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) spectroscopy and computational techniques. Theoretical calculation results indicated the binding ratio of the probe to Cu2+ is 2 : 1 and the binding constant was obtained as 1.72 × 10 8 M-1. Cu2+ concentration can be detected with the detection limit of 16 nM. Free Cu2+ concentration released from the metallothionein-Cu complex at different pH values was detected. Cu2+ concentration in real water and tea samples was also detected, and the results were consistent with the ones monitored by atomic absorption spectrometer. Because of the exceedingly small K sp value of CuS (1.27 × 10-36), S2- can sequester Cu2+ from HDSGWEVHH to restore the tryptophan (W) fluorescence. Thus the HDSGWEVHH-Cu2+ complex can also be used for S2- detection. The S2- concentrations can be monitored with a detection limit of 19 nM. The assay is also amenable to measurement of S2- concentration in pure water samples. Thus the probe designed herein is sensitive, label free, low cost, and environmentally friendly for Cu2+ and S2- determination in aqueous solutions.

MicroRNA­144 suppresses aggressive phenotypes of tumor cells by targeting ANO1 in colorectal cancer.

The aim of the present study was to research the mechanism of action of microRNA­144 (miR­144) in colorectal cancer (CRC) and its role in tumor progression. It was demonstrated that miR­144 was downregulated and anoctamin 1 (ANO1) expression was upregulated in CRC. The expression of ANO1 was negatively associated with that of miR­144 in CRC. The present study indicated that upregulated expression of ANO1 was associated with poor differentiation and advanced tumor­node­metastasis stage. It was verified that upregulation of ANO1 expression activated the epidermal growth factor receptor/extracellular signal­regulated kinase signaling pathway. It was also demonstrated that miR­144 exerts strong tumor­inhibiting effects by targeting ANO1. Therefore, miR­144 may have potential as a prognostic marker or therapeutic target for CRC.