Zhenghua Zhang

An ‘activatable’ aptamer-based fluorescence probe for the detection of HepG2 cells

It is significant to develop a probe with sensitivity and specificity for the detection of cancer cells. The present study aimed to develop an ‘activatable’ aptamer-based fluorescence probe (AAFP) to detect cancer cells and frozen cancer tissue. This AAFP consisted of two fragments: aptamer TLS11a that targets HepG2 cells, and two short extending complementary DNA sequences with a 5′- and 3′-terminus that make the aptamer in hairpin structure a capable quencher to fluorophore. The ability of the AAFP to bind specifically to cancer cells was assessed using flow cytometry, fluorescence spectroscopy and fluorescence microscopy. Its ability to bind to frozen cancer tissue was assessed using fluorescence microscopy. As a result, in the absence of cancer cells, AAFP showed minimal fluorescence, reflecting auto-quenching. In the presence of cancer cells, however, AAFP showed a strong fluorescent signal. Therefore, this AAFP may be a promising tool for sensitive and specific detection of cancer.

Graphene and Au NPs co-mediated enzymatic silver deposition for the ultrasensitive electrochemical detection of cholesterol

Cholesterol is an essential ingredient in mammals, and serum cholesterol is a major component of atherosclerotic plaques. The level of cholesterol in human serum has become an important index for clinical diagnosis and prevention of cardiovascular disease. In this paper, a simple and ultrasensitive cholesterol biosensor based on graphene oxide (GO) and gold nanoparticles (Au NPs) co-mediated enzymatic silver deposition was designed by immobilizing cholesterol oxidase (CHOD), cholesterol esterase (CHER) and GO onto the surface of Au NPs modified screen-printed carbon electrode (SPE). Under the synergistic effect of CHER, CHOD and GO, the cholesterol was hydrolyzed to generate hydrogen peroxide, which can reduce the silver (Ag) ions in the solution to metallic Ag which deposited on the surface of Au NPs modified SPE. The ultrasensitive detection of cholesterol was achieved by anodic stripping voltammetry measurement of the enzymatically deposited Ag. Under optimal conditions, the anodic stripping peak current of Ag increased with the increasing cholesterol concentration in the range from 0.01μg/mL to 5000μg/mL with a limit of detection of 0.001μg/mL (S/N = 3). In addition, the ultrasensitive cholesterol biosensor exhibited higher specificity, acceptable reproducibility and excellent recoveries for cholesterol detection.

Mouse IP-10 Gene Delivered by Folate-modified Chitosan Nanoparticles and Dendritic/tumor Cells Fusion Vaccine Effectively Inhibit the Growth of Hepatocellular Carcinoma in Mice

Dendritic cells (DC) and tumor cell fusion vaccine (DC/tumor cell fusion vaccine) is considered an effective approach in cancer biotherapy. However, its therapeutic effects in early clinical trials have been suboptimal partially due to the immunosuppressive tumor environment. In this study, we used nanoparticles of folate (FA)-modified chitosan, a non-viral vector capable of targeting tumor cells with high expression of FA receptors. FA-chitosan nanoparticles were used as biological carriers for the expression plasmid of the mouse interferon-induced protein-10 (mIP-10) gene, a potent chemoattractant for cytotoxic T cells. The combination of FA-chitosan/mIP-10 and DC/tumor cell fusion vaccine against hepatocellular carcinoma (HCC) effectively inhibited the growth of implanted HCC tumors and prolonged the survival of mice. The combination therapy significantly reduced myeloid-derived suppressor cells (MDSC) in mouse spleen, local tumor, and bone marrow while increasing tumor-specific IFN-γ responses. Furthermore, the combination therapy significantly inhibited tumor cell proliferation while promoting their apoptosis. Taken together, our data illustrate that the mIP-10 enhances the anti-tumor effect of DC/tumor cell fusion vaccine by alleviating the immunosuppressive tumor environment.

Correction to: A Graphene Oxide-Based Fluorescent Aptasensor for the Turn-on Detection of CCRF-CEM

In the original publication of this article [1] the author Liping Zhong was omitted. In this correction article the author and the corresponding details are provided. The publisher apologizes to the readers and authors for the inconvenience.

Recent Progress of Wnt Pathway Inhibitor Dickkopf-1 in Liver Cancer

Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2. The expression of DKK-1 is regulated by p53, V-Myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), β-catenin, etc. Ectopic expression of DKK-1 can inhibit cell proliferation, or induce apoptosis with apoptosis enhancing factors. DKK-1 is low-expressed in many tumors, but overexpressed in others. Growing evidences show that DKK-1 plays complex and different roles in tumorigenesis, tumor progression and metastasis of different cancers. We herein review the recent progress in the expression and function of DKK-1 in hepatocellular carcinoma.

Generation of a Graft versus Anticancer Immune Response Through Skin Allograft with Tumor.

Effector memory T cells (TEM) are a subset of memory T cells which play an important role in stimulation of adaptive immunity. Although they are associated with multiple immune responses, the antitumor effect of TEM is not clearly understood. In this research, generation of anti-tumor TEM was induced through skin allografts in C57BL/6 mice with B16 melanoma. We observed that the growth of tumor tissues in C57BL/6 mice treated with allografts was interrupted. Furthermore, the survival time for the treated mice was prolonged along with increased serum levels for CXCL9, CXCL10 and INF-γ. Additionally, the concentrations of TEM in the spleens, lymph nodes and tumor tissues were markedly elevated in allografts treated mice. The tumor cell proliferation and tissue growth were suppressed in C57BL/6 mice with B16 melanoma induced by allografts, upon tail vein injection of purified TEM. These results demonstrate that skin allografts promote the generation of anti-tumor TEM in C57BL/6 mice with B16 melanoma, which emphasize the strong promise of TEM stimulation using allografts transplants in effective tumor immunotherapy.

Towards an Effective Management on the Teaching and Learning of Accounting in Simple and Rapid Colorimetric Bio-sensing of Alpha-fetoprotein Using Aptamer and Unmodified Gold Nanoparticles

A simple and rapid colorimetric method for determination of alpha-fetoprotein (AFP) has been developed here using specific aptamers and free gold nanoparticles (AuNPs). In the absence of AFP, the free aptamers prevent aggregation of AuNPs in a high salt environment, which cause the mixed solution remain red. Conversely, when there are existing AFP in colorimetric system, the aptamers is consumed to decrease, forming aptamer-AFP complex. AuNPs were aggregated due to losting the protection from aptamers in the high salt solution. The color of the solution turns to blue at this time. Subsequently, a color change of red-to-blue can be observed by the naked eye with the increasing of AFP. The linear response range for AFP was 10 to 2000 ng/ml and the detection limit was 5 ng/ml. This colorimetric biosenser does not require any modification, and its composition is cheap and easy to obtain. In addition, this proposed colorimetric method is also used in simulative hepatocellular carcinoma (HCC) serum samples and showed good feasibility, holding great potential for preliminary screening of serum of HCC in the future.

Collagen I enhances the efficiency and anti-tumor activity of dendritic-tumor fusion cells

ABSTRACT Low fusion efficiency and nominal activity of fusion cells (FCs) restrict the clinical application of dendritic cell (DC)/tumor fusion cells. Collagen I (Col I) is an interstitial collagen with a closely-knit structure used to repair damaged cell membranes. This study evaluated whether Col I could improve the fusion efficiency of polyethylene glycol (PEG)-induction and enhance the immunogenicity of fusion vaccine. DC/B16 melanoma and controlled DC/H22 hepatoma cell fusions were induced by PEG with or without Col I. Col I/PEG treatment increased the levels of DC surface molecules and the secretion of lactate, pro- and anti-inflammatory cytokines in fusion cells. Col I/PEG-treated FCs enhanced T-cell proliferation and cytotoxic T lymphocyte activity. The Col I-prepared fusion vaccine obviously suppressed tumor growth and prolonged mice survival time. Thus Col I treatment could significantly improve the efficiency of PEG-induced DC/tumor fusion and enhance the anticancer activity of the fusion vaccine. This novel fusion strategy might promote the clinical application of DC/tumor fusion immunotherapy.