Th1 immune response induction by biogenic selenium nanoparticles in mice with breast cancer: preliminary vaccine model

Background: tumor associated antigens can be viably used to enhance host immune response

Objectives: the immunomodulatory effect of biogenic selenium nanoparticles [SeNPs] was compared between treated and untreated mice with crude antigens of 4T1 cells

Materials and Methods: female inbred BALB/c mice [60] were injected by cancinogenic 4T1 cells causing breast cancer. After 10 days, all tumor bearing mice were divided into 4 groups. Group 1 was daily provided oral PBS and injected by the same buffer after tumor induction and was considered as control. Group 2 received only 100 [micro]g/day SeNPs as an oral supplement for 30 days. Group 3 was only injected with 4T1 cells crude antigens with nil supplementation of SeNPs. Group 4 animals were supplemented 100 [micro]g/day SeNPs for 30 days and simultaneously injected with crude antigens of 4T1 cells. All antigens or PBS injections were introduced at 7, 14 and 28 days following tumor induction. Oral PBS and SeNPs supplementation initiated from the first day of tumor induction and continued up to 30 days. During tumor growth, animal weights and survival rates were monitored and at the end of the study the concentrations of different cytokines and DTH responses were measured

Results: data clearly showed that the levels of cellular immunomodulatory components [granzyme B, IL-12, IFN-[lambada], and IL-2] significantly increased [P < 0.05] in mice treated with both SeNPs and crude antigens of 4T1 cells in comparison to the other groups. In contrast, the levels of TGF-[beta] in these mice decreased

Conclusions: although SeNPs showed a noticeable boosting effect for the immune response in mice bearing tumor exposed to crude antigens of 4T1 cells, further complementary studies seem to be inevitable

Antimicrobial activities of three medicinal plants and investigation of flavonoids of Tripleurospermum disciforme

Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used as disinfectant agents and for treatment of some disease in folk medicine of Iran. The antimicrobial effects of different fractions of seeds extract of S. securidaca, petals extract of R. damascena and aerial parts extract of T. disciforme were examined against some gram positive, gram negative and fungi by cup plate diffusion method. The petroleum ether and chloroform fractions of S. securidaca showed antibacterial activities against Staphylococcus aureus and Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects. R. damascena petals extract demonstrated antibacterial activities against Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects only against S. aureus and S. epidermidis. None of the fractions had any antifungal activities. Therefore, present study confirmed utility of these plants as disinfectant agents. Six flavonoids were isolated from T. disciforme: Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T. disciforme are reported for the first time

Two matrix metalloproteinase inhibitors from scrophularia striata boiss

Many species belonging to the Scrophularia genus have been used since ancient times as folk remedies for many medical conditions such as scrofulas, scabies, tumors, eczema, psoriasis, inflammations. The aim of this study was to characterize the matrix metalloproteinases [MMPs] inhibitor compounds of the Scrophularia striata extract by bio-guide fractionation. The aerial parts of S. striata were collected and different extracts were sequentially prepared with increasingly polar solvents. The MMPs inhibitory activity of the crude extract and its fractions were evaluated by the Zymoanalysis method. The pure compounds were purified from the active fraction by chromatography methods. Chemical structures were deduced by nuclear magnetic resonance and mass spectrometry. Two active compounds [acteoside and nepitrin] were identified by bio-guide fractionation. The inhibitory effects of nepitrin and acteoside at 20 Micro g/ml were about 56 and 18 percent, respectivly. The inhibitory effects of acteoside at 80 Micro g/ml were increased to about 73 percent. In summary, the results suggest that nepitrin effectively inhibited MMPs inhibitory activity at low concentrations, whereas acteoside showed inhibition at high concentrations

Combined application of sub-toxic level of silver nanoparticles with low powers of 2450 MHz microwave radiation lead to kill Escherichia coli in a short time

Electromagnetic radiations which have lethal effects on the living cells are currently also considered as a disinfective physical agent. In this investigation, silver nanoparticles were applied to enhance the lethal action of low powers [100 and 180 W] of 2450 MHZ electromagnetic radiation especially against Escherichia coli ATCC 8739. Silver nanoparticles were biologically prepared and used for next experiments. Sterile normal saline solution was prepared and supplemented by silver nanoparticles to reach the sub-inhibitory concentration [6.25microg/mL]. Such diluted silver colloid as well as free-silver nanoparticles solution was inoculated along with test microorganisms, particularly E. coli. These suspensions were separately treated by 2450 MHz electromagnetic radiation for different time intervals in a microwave oven operated at low powers [100 W and 180 W]. The viable counts of bacteria before and after each radiation time were determined by colony-forming unit [CFU] method. Results showed that the addition of silver nanoparticles significantly decreased the required radiation time to kill vegetative forms of microorganisms. However, these nanoparticles had no combined effect with low power electromagnetic radiation when used against Bacillus subtilis spores. The cumulative effect of silver nanoparticles and low powers electromagnetic radiation may be useful in medical centers to reduce contamination in polluted derange and liquid wastes materials and some devices

Hydroxyl capped silver-gold alloy nanoparticles: characterization and their combination effect with different antibiotics against Staphylococcus aureus

Metal nanoparticles [NPs] offer a wide variety of potential applications in pharmaceutical sciences due to the unique advances in nanotechnology research. In this work, bimetal Ag-Au alloy NPs were prepared and their combinations with other antibiotics were tested against Staphylococcus aureus. Firstly, Ag-Au alloy NPs with Au/Ag molar ratio of 1:1 was fabricated and was purified by agarose gel electrophoresis system. The morphology and size of the purified NPs were confirmed by transmission electron microscopy. Chemical composition and surface chemistry of these NPs were studied with atomic absorption spectophotometry and Fourier transforms infrared spectroscopy, respectively. The size of purified Ag-Au alloy NPs was less than 200 nm. Also the presence of organic compounds with a hydroxyl residue was detected on the surface of these purified NPs. In next step the effect of purified Ag-Au alloy NPs on the antibacterial activity of different antibiotics was evaluated at sub-inhibitory content [5 microg/disk] using disk diffusion method against S. aureus. Ag NPs and Au NPs were also tested at same content [5 microg] using mentioned method. The most enhancing effect of Ag-Au alloy NPs was observed for penicillin G and piperacillin. No enhancing effects on the antibacterial activity of different antibiotics were observed at 5 microg/disk for the mono-metal nanoparticles [Ag NPs and Au NPs] against S. aureus. These results signify that the Ag-Au alloy NPs potentiates the antimicrobial action of certain antibiotics suggesting a possible utilization of this nano material in combination therapy against resistant S. aureus

Green synthesis of silver nanoparticles: the reasons for and against Aspergillus parasiticus

The enzymatic activity of fungi has recently inspired the scientists with re-explore the fungi as potential biofactories rather than the causing agents of humans and plants infections. In very recent years, fungi are considered as worthy, applicable and available candidates for synthesis of smaller gold, silver and other nano-sized particles. A standard strain of Aspergillus parasiticus was grown on a liquid medium containing mineral salt. The cell-free filtrate of the culture was then obtained and subjected to synthesize SNPs while expose with 1mM of AgNO[3]. Further characterization of synthesized SNPs was performed afterward. In addition, antifungal activity of synthesized SNPs was evaluated against a standard strain of Candida albicans. The reduction of Ag+ ions to metal nanoparticles was investigated virtually by tracing the color of the solution which turned into reddish-brown after 72 h. The UV-vis spectra demonstrated a broad peak centering at 400 nm which corresponds to the particle size much less than 70 nm. The results of TEM demonstrated that the particles were formed fairly uniform, spherical, and small in size with almost 90% in 5-30 nm range. The zeta potential of silver nanoparticles was negative and equal to 15.0 which meets the quality and suggested that there was not much aggression. Silver nanoparticles synthesized by A. parasiticus showed antifungal activity against yeast strain tested and exhibited MIC value of 4 microg/mL. The filamentous fungus, A. parasiticus has successfully demonstrated potential for extra cellular synthesis of fairly monodispersed, tiny silver nanoparticles

Effect of oral supplementation of biogenic selenium nanoparticles on white blood cell profile of BALB/c mice and mice exposed to X-ray radiation

Radiation therapy is an effective method used for treatment of many types of cancers. However, this method can cause unwanted side effects such as bone marrow suppression. In this study, the effect of oral administration of biogenic selenium nanoparticles [SeNPs] on total and differentiated white cells profile of BALB/c mice exposed to X-ray radiation was investigated and compared with non-irradiated mice. Sixty female BALB/c mice between six to eight weeks olds were divided into 4 test and control groups in two categories of normal and irradiated mice. In normal mice SeNPs administration was started from the day 0 and followed for a month. Irradiated mice were divided into three groups and were exposed to doses of 2, 4 and 8 Gy. After 72 hr of irradiation, the SeNPs treatment was started and continued for a month. Total and differentiated blood cells counts of both irradiated and non-irradiated groups were monitored during 30 days and the obtained results were compared. Also, the deposition of Se in different tissues and blood serum of normal mice was determined in normal mice after 30 days period of supplementation. In normal mice an increase in the count of neutrophils was observed after 30 days of supplementation. In irradiated mice, SeNPs supplementation led to increase in both lymphocytes and neutrophils counts especially in mice exposed to 2 and 4 Gys radiation. Radiotherapy is categorized as an invasive method which can cause tissue damage and suppress the host immune defense. A restore of lymphocytes which was observed after SeNPs supplementation in irradiated mice can be highly interesting and provide cellular immunity against malignant diseases or other bacterial or fungal infections after radiotherapy

Isolation and characterization of a fungus for extracellular synthesis of small selenium nanoparticles

The use of biogenic selenium nanoparticles for various purposes is going to be an issue of considerable importance; thus, appropriate simple methods should be developed and tested for the synthesis and recovery of these nanoparticles. In this study, a fungus was isolated from a soil sample, identified as Aspergillus terreus and used for extracellular synthesis of selenium nanoparticles [Se NPs]. UV-Vis spectroscopy and energy dispersive X-ray spectrum studies were carried out to confirm Se NPs formation within 60 min. Dynamic light scattering and scan electron microscopic methods were also used to characterize both size and shapes of the Se NPs. The results show that spherical particles with average size of 47 nm were formed by adding a culture supernatant of A. terreus to selenium ions solution. This approach appears to be an easy and appropriate method for extracellular synthesis of small Se NPs. Extracellular synthesis of small Se NPs has not been reported yet

Sub-Inhibitory concentration of biogenic selenium nanoparticles lacks post antifungal effect for Aspergillus niger and Candida albicans and stimulates the growth of Aspergillus niger

The antifungal activity of selenium nanoparticles [Se NPs] prepared by Klebsiella pneumoniae has been reported previously for different fungi. In the present study, freshly prepared Se NPs produced by K. pneumoniae were purified and characterized by transmission electron microscopy and Energy-Dispersive X-ray spectroscopy [EDS] and its post antifungal effects for two fungi were evaluated. The minimum inhibitory concentrations [MICs] ofSe NPs, determined by serial dilution were 250 microg/ml for Aspergillus niger and 2,000 microg/ml for Candida albicans. The effect of exposure of A. niger and C. albicans to Se NPs on later growth was evaluated by incubating the fungi for 1 hour at 25°C in media containing 0, 1, 2 and 4 x MIC of Se NPs and diluting the cultures 100 times with Se free medium. The kinetics of growth of the fungi in control cultures and in non-toxic Se NPs concentration of, 0.01 x MIC, 0.02 x MIC or 0.04 x MIC were measured. The exposure of A niger and C. albicans to 2 and 4 x MIC of Se NPs stimulated the growth of both fungi in the absence of toxic concentrations of Se. The strongest stimulation was observed for A. niger. It is concluded that exposure to high concentration of the Se NPs did not have any post-inhibitory effect on A. niger and C. albicans and that trace amounts of this element promoted growth of both fungi in a dose- dependent-manner. The role of nanoparticles serving as needed trace elements and development of microorganism tolerance to nanoparticles should not be dismissed while considering therapeutic potential

[Minimum inhibitory concentration of ciprofloxacin in combination with hexahydroquinoline derivatives against Staphylococcus aureus]

Staphylococcus aureus is the most common pathogen responsible for skin and soft tissue infections worldwide. Methicillin-resistant S. aureus is a major cause of both nosocomial and community acquired infections. The emergence of antimicrobial-resistant S. aureus is of global concern. Fluoroquinolone antimicrobials including ciprofloxacin, levofloxacin, and moxifloxacin are used to treat skin and soft tissue infections due to S. aureus. Emergence of ciprofloxacin resistance has increased in community acquired methicillin-resistant S. aureus strains. The aim of this study was to evaluate the minimum inhibitory concentration of ciprofloxacin and hexahydroquino-line derivatives against methicillin- and ciprofloxacin-resistant S. aureus. Identification of S. aureus was performed by routine microbiological tests in the Department of Pathobiology in Winter 2012. The susceptibility of S. aureus strains to both methicillin and ciprofloxacin was examined by the Kirby-Bauer disk-diffusion method. The minimum inhibitory concentration of ciprofloxacin, hexahydroquinoline derivatives and their combination were separately determined by broth microdilution method against methicillin- and ciprofloxacin-resistant S. aureus. The minimum inhibitory concentration of ciprofloxacin decreased in the presence of hexahydroquinolinein derivatives in comparison with ciprofloxacin alone. This study showed that hexahydroquinoline derivatives enhance the antibacterial effect of ciprofloxacin against methicillin- and ciprofloxacin-resistant S. aureus. Therefore, these derivatives could be used as inhibitors of antibiotic resistance in combination therapies. This enhancement may be related to the inhibitory effect of hexahydroquinoline derivatives on the expression of antibiotic efflux pump in the bacteria. However, the structural features of a fluoroquinolone that determine whether it is affected by efflux transporters are not fully defined.

Derivation of adipocytes from human endometrial stem cells [EnSCs]

Due to increasing clinical demand for adipose tissue, a suitable cell for reconstructive adipose tissue constructs is needed. In this study, we investigated the ability of Human Endometrial-derived stem cells [EnSCs] as a new source of mesenchymal stem cells to differentiate into adipocytes. EnSCs are the abundant and easy available source with no immunological response, for cell replacement therapy. Single-cell suspensions of EnSCs were obtained from endometrial tissues from 10 women experiencing normal menstrual cycles, and were cultured at clonal density [10 cells/cm[2]] or limiting dilution. Endometrial mesenchymal stem cell markers were examined flow cytometry. These cells were treated with adipogenicinducing medium for 28 days. The adipogenic differentiation of the EnSC was assessed by cellular morphology and further confirmed by Oil Red O staining and RTPCR. The BM-MSC differentiated into adipocytes in the presence of adipogenic stimuli for 3 weeks. The flow cytometric analysis showed that the cells were positive for CD90, CD105, CD146 and were negative for CD31, CD34.We showed that the key adipocytes marker PPARa was expressed in mRNA level after 28 days post treatment [PT]. According to our finding, it can be concluded that EnSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage

enhancing effect of gold nanoparticles on the lethal action of 2450 mhz electromagnetic radiation in microwave oven

Today, there is an increasing interest in the use of metal nanoparticles in health sciences. Amongst all nanoparticles, the gold nanoparticles have been known to kill the cancer cells under hyperthermic condition by near-infrared frequency electromagnetic waves. On the other hand, although there are different physiochemical methods for disinfection of microbial pollution, however applications of irradiated gold nanoparticles against microorganisms have not yet been investigated. In this study, gold nanoparticles were prepared using D-glucose and characterized [particle size <26 nm]. In the next step, the enhancing effect of the non toxic level of gold nanoparticles [50 microg/mL] on the antimicrobial activity of 2450 MHz electromagnetic radiation generated at a microwave oven operated at low power [100 W], was investigated by time-kill course assay against Staphylococcus aureus [S. aureus] ATCC 29737. The results showed that application of gold nanoparticles can enhance the lethal effect of low power microwave in a very short exposure time [5 s]

Cytotoxic activities of silver nanoparticles and silver ions in parent and tamoxifen-resistant T47D human breast cancer cells and their combination effects with tamoxifen against resistant cells

Studies on biomedical applications of nanoparticles are growing with a rapid pace. In medicine, nanoparticles may be the solution for multi-drug-resistance which is still a major drawback in chemotherapy of cancer. In the present study, we investigated the potential cytotoxic effect of silver nanoparticles [Ag NPs] and silver ions [Ag[+]] in both parent and tamoxifen-resistant T47D cells in presence and absence of tamoxifen. Ag NPs were synthesized [< 28 nm] and MTT assay was carried out. The associated IC[50] values were found to be: 6.31 micro g/ml for Ag NPs/parent cells, 37.06 micro g/ml for Ag NPs/tamoxifen-resistant cells, 33.06 micro g/ml for Ag[+]/parent cells and 10.10 micro g/ml for Ag[+]/resistant cells. As a separate experiment, the effect of subinhibitory concentrations of Ag NPs and Ag[+] on the proliferation of tamoxifen-resistant cells was evaluated at non-toxic concentrations of tamoxifen. Our results suggested that in noncytotoxic concentrations of silver nanomaterials and tamoxifen, the combinations of Ag[+]-tamoxifen and Ag NPs-tamoxifen are still cytotoxic. This finding may be of great potential benefit in chemotherapy of breast cancer; since much lower doses of tamoxifen may be needed to produce the same cytotoxic effect and side effects will be reduced

Green synthesis of small silver nanoparticles using geraniol and its cytotoxicity against fibrosarcoma-Wehi 164

Many reports have been published about the biogenesis of silver nanoparticles using several plant extracts such as Pelargonium graveolens [P.graveolens-geranium] and Azadirachta indica [neem] but the capacity of their natural reducing constituents to form silver nanoparticles has not yet been studied. In this research the synthesis of silver nanoparticles using geraniol has been investigated. We successfully synthesized uniformly dispersed silver nanoparticles with a uniform size and shape in the range of 1 to 10 nm with an average size of 6 nm. Also the cytotoxicity of the prepared silver nanoparticles was investigated using a cancer cell line [Fibrosarcoma-Wehi 164]. The cytotoxicity analysis of the sample shows a direct dose-response relationship; cytotoxicity increased at higher concentrations. At concentration of 1 pg/ml, silver nanoparticles was able to inhibit the cell line's growth by less than 30%. Conversly, the presence of 5 pg/m/of silver nanoparticlse significantly inhibited the cell line's growth [> 60%]. The concentration necessary to produce 50% cell death was 2.6 microg/m/for this silver nanoparticles preapared with geraniol