Targeting delivery of lipocalin 2-engineered mesenchymal stem cells to colon cancer in order to inhibit liver metastasis in nude mice

One of the major obstacles in cancer therapy is the lack of anticancer agent specificity to tumor tissues. The strategy of cell-based therapy is a promising therapeutic option for cancer treatment. The specific tumor-oriented migration of mesenchymal stem cells (MSCs) makes them a useful vehicle to deliver anticancer agents. In this study, we genetically manipulated bone marrow-derived mesenchymal stem cells with their lipocalin 2 (Lcn2) in order to inhibit liver metastasis of colon cancer in nude mice. Lcn2 was successfully overexpressed in transfected MSCs. The PCR results of SRY gene confirmed the presence of MSCs in cancer liver tissue. This study showed that Lcn2-engineered MSCs (MSC-Lcn2) not only inhibited liver metastasis of colon cancer but also downregulated the expression of vascular endothelial growth factor (VEGF) in the liver. Overall, MSCs by innate tropism toward cancer cells can deliver the therapeutic agent, Lcn2, and inhibit cancer metastasis. Hence, it could be a new modality for efficient targeted delivery of anticancer agent to liver metastasis. © 2015, International Society of Oncology and BioMarkers (ISOBM)

In vitro effect of nanosilver toxicity on fibroblast and mesenchymal stem cell lines

Nanotechnology presents countless opportunities to develop new and improved consumer products for the benefit of the society . A most prominent nanoproduct is nanosilver. Nanosilver particles are generally smaller than 100 nm and contain 20–15,000 silver atoms. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health. In the previous study we reported the cytotoxic of nanosilver on osteoblast G292 cancer cell line and the amount of IC50 determined as 3.42 µg/ml (Moaddab et al., Iran. Nano Lett., Vol. 1, No. 1, January 2011, pp. 11-16). The purpose of the present study is to assess the biological assay of nanosilver on two normal cell lines of fibroblast (HF2), and mesenchymal stem cells . The effect of nanosilver on these cells is evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. The results demonstrate a concentration-dependent toxicity for the cells tested, and IC50 was determined as 6.33, and 6.68 µg/ml in mesenchymal stem cell, and fibroblast HF2, respectively. There is no significant difference between the 24 h and 48 h of cells exposure to nanosilver. The results show that Nano-Ag possesses low toxicity to normal cells and can display potential application in cancer chemoprevention and chemotherapy

Neutrophil Gelatinase-Associated Lipocalin induces the expression of heme oxygenase-1 and superoxide dismutase 1, 2

Lipocalin-2 (Lcn2, NGAL) is a member of the lipocalin super family with diverse function such as the induction of apoptosis, the suppression of bacterial growth, and modulation of inflammatory response. Much interest has recently been focused on the physiological/pathological role of the lipocalin-2 that is considered to be a novel protective factor against oxidative stress. However, its precise biological roles in this protection are not fully understood. In this report we intended to test the effect of lipocalin-2 on the expression of heme oxygenase (1, 2) and superoxide dismutase (1, 2) which are two strong antioxidants. NGAL was cloned to pcDNA3.1 plasmid by using genetic engineering method. The recombinant vector was transfected to CHO and HEK293T to establish stable cell expressing NGAL and the expression of HO-1, 2 and SOD1, 2 were compared with appropriate controls byRT-PCR and western blot. On the other hand, expression of NGAL was suppressed by siRNA transfection in order to study the effect of lipocalin-2 on mentioned genes/proteins. The results showed that the expression of HO-1 and SOD 1, 2 enzymes were higher in cells expressing recombinant lipocalin-2 compared with the control cells. Although the expression of HO-1 was lower in NGAL silencing cells, the expression of SOD1 and SOD2 were higher. Our data suggest that NGAL is a potent inducer of HO-1 and somewhat SOD1 and SOD2 and it appears that part of antioxidant property of NGAL could be attributed to the induction of HO-1and SOD 1, 2. © Cell Stress Society International 2009

SYNTHESIS, MICROSTRUCTURE AND MECHANICAL PROPERTIES OF Mg - 5Zn - 0.3Ca/nHA NANOCOMPOSITES

Recently, magnesium and its alloys have attracted great attention for use as biomaterial due to their good mechanical properties and biodegradability in the bio environment. In the present work, nanocomposites of Mg - 5Zn - 0.3Ca/ nHA were prepared using a powder metallurgy method. The powder of Mg, Zn and Ca were firstly blended, then four different mixtures of powders were prepared by adding nHA in different percentages of 0, 1, 2.5 and 5 %wt. Each mixture of powder separately was fast milled, pressed, and sintered. Then, the microstructure and mechanical properties of the fabricated nanocomposites were investigated. The XRD profile for nanocomposites showed that the intermetallic phases of MgZn2, MgZn5.31 and Mg2Ca were created after sintering and the SEM micrographs showed that the grain size of nanocomposite reduced by adding the nHA. The nano composite with 1wt. % nHA increased the density of Mg alloy from 1.73 g/cm3 to 1. 75 g/cm3 by filling the pores at the grain boundaries. The compressive strength of Mg alloy increased from 295MPa to 322, 329 and 318MPa by addition of 1, 2.5 and 5wt. % nHA, respectively

The effect of swelling agent on the pore characteristics of mesoporous hydroxyapatite nanoparticles

The effect of swelling agent on the physicochemical properties of mesoporous hydroxyapatite particles synthesized by self-assembly process has been investigated. Cetyl trimethylammonium bromide (CTAB) and 1-dodecanethiol were used as soft template and swelling agent respectively. The results of the field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), simultaneous thermal analysis (STA), Brunauer-Emmett-Teller (BET) surface area, small-angle X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) assessments revealed that in the case of low concentration, 1-dodecanethiol performed as swelling agent and caused an increase in the pore size. However, at higher concentrations it led to the formation of microemulsion and foamy structures. The optimum swelling agent: surfactant mass ratio in synthesis of mesoporous hydroxyapatite particles with high pore volume was determined to be around 2.1 in this study

Camelid antivenom development and potential in vivo neutralization of Hottentotta saulcyi scorpion venom

Scorpion envenoming is a serious health problem which can cause a variety of clinical toxic effects. Of the many scorpion species native to Iran, Hottentotta saulcyi is important because its venom can produce toxic effects in man. Nowadays, antivenom derived from hyper immune horses is the only effective treatment for sever scorpion stings. Current limitations of immunotherapy urgently require an efficient alternative with high safety, target affinity and more promising venom neutralizing capability. Recently, heavy chain-only antibodies (HC-Abs) found naturally in camelid serum met the above mentioned advantages. In this study, immuno-reactivities of polyclonal antibodies were tested after successful immunization of camel using H. saulcyi scorpion crude venom. The lethal potency of scorpion venom in C57BL/6 mice injected intraperitoneally was determined to be 2.7 mg/kg. These results were followed by the efficient neutralization of lethal activity of H. saulcyi scorpion venom by injection of antivenom and purified IgG fractions into mice intraperitonelly or intravenously, respectively. HC-Ab camelid antivenom could be considered as a useful serotherapeutics instead of present treatment for scorpion envenomation. © 2016 Published by Elsevier Ltd