miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126(*), a microRNA pair derived from a single precursor, independently suppress the sequential recruitment of mesenchymal stem cells and inflammatory monocytes into the tumour stroma to inhibit lung metastasis by breast tumour cells in a mouse xenograft model.

Quantitative research of histone H3 acetylation levels of human hepatocellular carcinoma cells.

Background: Core histone H3 is a highly conserved protein in the cell nucleus, it goes through various post-translational modifications easily, and the state of the acetylation has clinical diagnostic significance in prostate cancer, breast cancer, lung cancer and other diseases.

Results: In this work, the combinatorial method of chromatographic separation, methylation isotope labeling and LTQ-Orbitrap(®) MS was employed to quantify the acetylation sites of histone H3 separately within normal liver cells L02 and hepatocellular carcinoma (HCC) cells HepG2, HCC metastasis cells 97H and HCC cells HepG2, high HCC metastasis potential cells LM3 and low HCC metastasis potential cells 97L. In comparison with the quantitative results of HepG2 and L02, the amounts of five acetylated and methylated peptides were found decreased.

Boronic acid-functionalized detonation nanodiamond for specific enrichment of glycopeptides in glycoproteome analysis.

Here we present the novel functionalization of detonation nanodiamond (dND) with amino-phenyl boronic acid (APBA) assisted by poly-L-lysine (PL) and PEG-diglycolic acid (PEG) (dND-p-APBA). With the assistance of biocompatible poly-L-lysine and PEG, dND-p-APBA particles show good dispersibility in aqueous solution and plentiful boronic acid functional groups on the surface, which make it a novel material promising for glycoproteome. The dND-p-APBA particles demonstrate highly specific and efficient capture of glycopeptides from complex samples.

A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer.

Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate myeloid cell mobilization from the bone marrow, leading to activation of the angiogenic process, as well as accumulation of macrophages and neutrophils in the tumor site. Neutralizing antibodies against PK2 were shown to display potent anti-tumor efficacy, illustrating the potential of PK2-antagonists as therapeutic agents for the treatment of cancer.

Specific and efficient N-propionylation of histones with propionic acid N-hydroxysuccinimide ester for histone marks characterization by LC-MS.

Histones participate in epigenetic regulation via a variety of dynamic posttranslational modifications (PTMs) on them. Mass spectrometry (MS) has become a powerful tool to investigate histone PTMs. With the bottom-up mass spectrometry approach, chemical derivatization of histones with propionic anhydride or deuterated acetic anhydride followed by trypsin digestion was widely used to block the hydrophilic lysine residues and generate compatible peptides for LC-MS analysis.

Radioisotope post-labeling upconversion nanophosphors for in vivo quantitative tracking.

Lanthanide based upconversion nanophosphors (UCNPs) attracted increasing attention for potential applications in bioimaging, while its in vivo behaviors are not clear until now due to no available quantification imaging tools. Herein, we developed a unique rare-earth cation-exchange-based postlabelling method to introduce (153)Sm into the lattice of UCNPs, providing this (153)Sm-postlabeling UCNP having bifunction of radioactive property and upconversion luminescence under excitation at 980 nm laser. This (153)Sm-postlabelling method shows rapid treatment time of <1 min, high labeling yield of >99%, and without usage of organic solvents.

First proteomic exploration of protein-encoding genes on chromosome 1 in human liver, stomach, and colon.

The launch of the Chromosome-Centric Human Proteome Project provides an opportunity to gain insight into the human proteome. The Chinese Human Chromosome Proteome Consortium has initiated proteomic exploration of protein-encoding genes on human chromosomes 1, 8, and 20. Collaboration within the consortium has generated a comprehensive proteome data set using normal and carcinomatous tissues from human liver, stomach, and colon and 13 cell lines originating in these organs.

Proteome atlas of human chromosome 8 and its multiple 8p deficiencies in tumorigenesis of the stomach, colon, and liver.

Chromosome 8, a medium-length euchromatic unit in humans that has an extraordinarily high mutation rate, can be detected not only in evolution but also in multiple mutant diseases, such as tumorigenesis, and further invasion/metastasis. The Chromosome-Centric Human Proteome Project of China systematically profiles the proteomes of three digestive organs (i.e.

Proteomic profiling of expression of proteasomal subunits from livers of mice treated with diethylnitrosamine.

The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Diethylnitrosamine is metabolized primarily in the liver by cytochrome P-450 and can cause DNA damage. The 26S proteasome is a large proteolytic complex that degrades ubiquitinated proteins, and regulates many physiological processes.

Highly specific revelation of rat serum glycopeptidome by boronic acid-functionalized mesoporous silica.

Although the specific profiling of endogenous glycopeptides in serum is highly inclined towards the discovery of disease biomarkers, studies on the endogenous glycopeptides (glycopeptidome) have never been conducted because of several factors. These factors include the high dynamic range of serum proteins, the inadequacy of traditional sample preparation techniques in proteomics for low-molecular-weight (LMW) proteins, and the relatively low abundances of glycopeptides. Boronic acid-functionalized mesoporous silica was synthesized in this study to overcome the limitations of the state-of-the-art methods for glycopeptidome research.

Therapeutic effects of astragaloside IV on myocardial injuries: multi-target identification and network analysis.

Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb used for cardiovascular diseases (CVD). In this work, we investigated the therapeutic mechanisms of AGS-IV at a network level by computer-assisted target identification with the in silico inverse docking program (INVDOCK). Targets included in the analysis covered all signaling pathways thought to be implicated in the therapeutic actions of all CVD drugs approved by US FDA.

Tumor-derived secretory clusterin induces epithelial-mesenchymal transition and facilitates hepatocellular carcinoma metastasis.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. Metastasis is the major concern that causes death in HCC. The goal of this study was to identify tumor-derived proteins in serum during HCC metastasis using an orthotopic xenograft tumor model and explore the role of key protein in HCC metastasis.

TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.

Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus (HBV) infection and development of PVTT. Mechanistically, elevated TGF-β activity, associated with the persistent presence of HBV in the liver tissue, suppresses the expression of microRNA-34a, leading to enhanced production of chemokine CCL22, which recruits regulatory T (Treg) cells to facilitate immune escape.

MicroRNA-1 inhibits proliferation of hepatocarcinoma cells by targeting endothelin-1.

Aims: MicroRNA-1 (miR-1) has been demonstrated as a tumor-suppressive miRNA, which shows a down-regulated pattern in several human malignancies including hepatocellular carcinoma (HCC). However, the pathophysiologic roles of miR-1 and their mechanisms in HCC tumorigenesis are still not totally elucidated.

Main Methods: Pre-miR-1 was cloned into pSuper plasmid to overexpress the miR-1 in hepatoma cells.

Comparative proteomic analysis of drug sodium iron chlorophyllin addition to Hep 3B cell line.

The human hepatoma 3B cell line was chosen as an experimental model for in vitro test of drug screening. The drugs included chlorophyllin and its derivatives such as fluo-chlorophyllin, sodium copper chlorophyllin, and sodium iron chlorophyllin. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method was used in this study to obtain the primary screening results.

Preparation of sandwich-structured graphene/mesoporous silica composites with C8-modified pore wall for highly efficient selective enrichment of endogenous peptides for mass spectrometry analysis.

In this study, sandwich-structured graphene/mesoporous silica composites (C8-modified graphene@mSiO(2)) were synthesized by coating mesoporous silica onto hydrophilic graphene nanosheets through a surfactant-mediated cocondensation sol-gel process. The newly prepared C8-modified graphene@mSiO(2) nanocomposites possess unique properties of extended plate-like morphology, good water dispersibility, highly open pore structure, uniform pore size (2.8 nm), high surface area (632 m(2)/g), and C8-modified-interior pore walls.

A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway.

Background And Purpose: Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia.

Proteomic study explores AGR2 as pro-metastatic protein in HCC.

Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors worldwide. The prognosis of patients with HCC still remains very dismal, mainly due to metastasis. We found that high-expression levels of AGR2 existed in metastatic HCC cell lines and patient samples.

Improved proteomic analysis pipeline for LC-ETD-MS/MS using charge enhancing methods.

Electron transfer dissociation (ETD) is a useful and complementary activation method for peptide fragmentation in mass spectrometry. However, ETD spectra typically receive a relatively low score in the identifications of 2+ ions. To overcome this challenge, we, for the first time, systematically interrogated the benefits of combining ion charge enhancing methods (dimethylation, guanidination, m-nitrobenzyl alcohol (m-NBA) or Lys-C digestion) and differential search algorithms (Mascot, Sequest, OMSSA, pFind and X!Tandem).

A novel quantitative proteomics workflow by isobaric terminal labeling.

Quantification by series of b, y fragment ion pairs generated from isobaric-labeled peptides in MS2 spectra has recently been considered an accurate strategy in quantitative proteomics. Here we developed a novel MS2 quantification approach named quantitation by isobaric terminal labeling (QITL) by coupling (18)O labeling with dimethylation. Trypsin-digested peptides were labeled with two (16)O or (18)O atoms at their C-termini in H(2)(16)O or H(2)(18)O.

Knockdown of nucleosome assembly protein 1-like 1 promotes dimethyl sulfoxide-induced differentiation of P19CL6 cells into cardiomyocytes.

Transplantation of cardiomyocytes derived from stem cells is a promising option for cardiac repair. However, how to obtain efficient cardiomyocytes from stem cells is still a great challenge. Understanding of the mechanism that regulates the cardiac differentiation of stem cells is necessary for the effective induction of cardiomyocytes.

Enhanced N-glycosylation site exploitation of sialoglycopeptides by peptide IPG-IEF assisted TiO2 chromatography.

Playing an important role in a broad range of biological and pathological processes, sialylation has been drawing wide interest. The efficient sialoglycopeptides enrichment methods are therefore attracting considerable attention. In this paper, we first compared two conventional enrichment methods, lectin and TiO(2), and analyzed their characteristics.

Proteolysis in microfluidic droplets: an approach to interface protein separation and peptide mass spectrometry.

A versatile microreactor protocol based on microfluidic droplets has been developed for on-line protein digestion. Proteins separated by liquid chromatography are fractionated in water-in-oil droplets and digested in sequence. The microfluidic reactor acts also as an electrospray ionization emitter for mass spectrometry analysis of the peptides produced in the individual droplets.

pH-controlled delivery of doxorubicin to cancer cells, based on small mesoporous carbon nanospheres.

Mesoporous carbon nanospheres (MCNs) with small diameters of ≈90 nm are developed as an efficient transmembrane delivery vehicle of an anticancer drug, doxorubicin (DOX). MCNs exhibit a high loading capacity toward DOX due to hydrophobic interactions and the supramolecular π stacking between DOX and the carbonaceous structures, on which the pH-dependent drug release are successfully achieved. Specifically, DOX can be loaded onto MCNs in basic solution and in a physiological pH range, while release occurs in acidic solution in its ionized state.