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Phloridzin (phlorizin or phloretin 2'-O-glucoside) is known for blocking intestinal glucose absorption. We have investigated the anticarcinogenic effect of phloridzin and its novel derivatives using human cancer cell lines. We have synthesised novel acylated derivatives of phloridzin with six different long chain fatty acids by regioselective enzymatic acylation using Candida Antarctica lipase B. The antiproliferative effects of the new compounds were investigated in comparison with the parent compounds, phloridzin, aglycone phloretin, the six free fatty acids and chemotherapeutic drugs (sorafenib, doxorubicin and daunorubicin) using human hepatocellular carcinoma HepG2 cells, human breast adenocarcinoma MDA-MB-231 cells and acute monocytic leukemia THP-1 cells along with normal human and rat hepatocytes. The fatty acid esters of phloridzin inhibited significantly the growth of the two carcinoma and leukemia cells while similar treatment doses were not toxic to normal human or rat hepatocytes. The antiproliferative potency of fatty esters of phloridzin was comparable to the potency of the chemotherapeutic drugs. The fatty acid esters of phloridzin inhibited DNA topoisomerases IIα activity that might induce G0/G1 phase arrest, induced apoptosis via activation of caspase-3, and decreased ATP level and mitochondrial membrane potential in HepG2 cells. Based on the high selectivity on cancer cells, decosahexaenoic acid (DHA) ester of phloridzin was selected for gene expression analysis using RT2PCR human cancer drug target array. Antiproliferative effect of DHA ester of phloridzin could be related to the down regulation of anti-apoptotic gene (BCL2), growth factor receptors (EBFR family, IGF1R/IGF2, PDGFR) and its downstream signalling partners (PI3k/AKT/mTOR, Ras/Raf/MAPK), cell cycle machinery (CDKs, TERT, TOP2A, TOP2B) as well as epigenetics regulators (HDACs). These results suggest that fatty esters of phloridzin have potential chemotherapeutic effects mediated through the attenuated expression of several key proteins involved in cell cycle regulation, DNA topoisomerases IIα activity and epigenetic mechanisms followed by cell cycle arrest and apoptosis.

Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy.

The current study investigated the effect and mechanisms of action of Liuwei Dihuang ethanol extract (LWDH-EE) on obesity and related metabolic phenotypes in male obese-prone CD rats. The rats were fed a high-fat diet and treated with 0 (obese control), 350 (EE350), or 700 (EE700) mg/kg/d of LWDH-EE in water once a day by gavage feeding for 10 weeks. The EE700 decreased body weight after 3 weeks of the treatment and the effect was maintained throughout the remaining study period. The EE700 also significantly reduced visceral fat and improved metabolic phenotypes by lowering the serum total cholesterol (T-C), non-high-density lipoprotein cholesterol, triacylglycerol, free fatty acids (FFA), and leptin levels. The EE350 reduced epididymal fat, serum T-C, and FFA but did not significantly affect other parameters. LWDH-EE dose-dependently increased fat and carbohydrate oxidations, energy expenditure, and the relative efficiency of fat oxidation for energy expenditure. EE350 and EE700 reduced food intake only in week 5 and did not affect the accumulative food intake in every week and the entire treatment period. Taken together, the results suggest that LWDH-EE is a potential therapeutic agent for the prevention of obesity possibly through a primary action of increasing energy metabolism and expenditure, along with a possible effect of decreasing energy intake.

One of the major problems that humanity has to face in the next 50 years is the energy crisis. The rising population, rapidly changing life styles of people, heavy industrialization and changing landscape of cities have increased energy demands, enormously. The present annual worldwide electricity consumption is 12 TW and is expected to become 24 TW by 2050, leaving a challenging deficit of 12 TW. The present energy scenario of using fossil fuels to meet the energy demand is unable to meet the increase in demand effectively, as these fossil fuel resources are non-renewable and limited. Also, they cause significant environmental hazards, like global warming and the associated climatic issues. Hence, there is an urgent necessity to adopt renewable sources of energy, which are eco-friendly and not extinguishable. Of the various renewable sources available, such as wind, tidal, geothermal, biomass, solar, etc., solar serves as the most dependable option. Solar energy is freely and abundantly available. Once installed, the maintenance cost is very low. It is eco-friendly, safely fitting into our society without any disturbance. Producing electricity from the Sun requires the installation of solar panels, which incurs a huge initial cost and requires large areas of lands for installation. This is where nanotechnology comes into the picture and serves the purpose of increasing the efficiency to higher levels, thus bringing down the overall cost for energy production. Also, emerging low-cost solar cell technologies, e.g. thin film technologies and dye-sensitized solar cells (DSCs) help to replace the use of silicon, which is expensive. Again, nanotechnological implications can be applied in these solar cells, to achieve higher efficiencies. This paper vividly deals with the various available solar cells, choosing DSCs as the most appropriate ones. The nanotechnological implications which help to improve their performance are dealt with, in detail. Additionally, the economic and ecological aspects of using nanotechnology are briefly introduced.

A rice-shaped TiO2-ZnO composite was prepared by electrospinning a mixture comprising the precursors of TiO2 and ZnO in polyvinyl acetate polymer dissolved in N,N-dimethyl acetamide. The electrospun nanofibers upon heat treatment in air resulted in collapse of the continuous fiber morphology and the formation of the rice-shaped TiO2-ZnO composite. The TiO2-ZnO composite was then treated with dilute acetic acid under hydrothermal conditions to etch ZnO from the TiO2-ZnO composite to get coral-shaped anisotropic TiO2. The structural anisotropy of TiO2 produced by the selective etching of ZnO resulted in a high surface area of 148 m(2) g(-1) for the TiO2. The initial and final materials were characterized by scanning electron microscopy, transmission electron microscopy, Raman and XPS spectroscopies, powder X-ray diffraction and BET surface area measurements. The utility of the anisotropic TiO2 in photovoltaics and photocatalysis was explored. Dye-sensitized solar cells fabricated using the TiO2 showed a conversion efficiency of 6.54% as against 4.8% for a control experiment with the rice-shaped TiO2. The anisotropic TiO2 also showed good photocatalysis in the degradation of methyl orange dye and phenol.

Composite nanofibrous scaffolds with various poly(ε-caprolactone) (PCL)/gelatin ratios (90:10, 80:20, 70:30, 60:40, 50:50 wt.%) were successfully electrospun using diluted acetic and ethyl acetate mixture. The effects of this solvent system on the solution properties of the composites and its electrospinning properties were investigated. Viscosity and conductivity of the solutions, with the addition of gelatin, allowed for the electrospinning of uniform nanofibers with increasing hydrophilicity and degradation. Composite nanofibers containing 30 and 40 wt.% gelatin showed an optimum combination of hydrophilicity and degradability and also maintained the structural integrity of the scaffold. Human mesenchymal stem cells (hMSCs) showed favorable interaction with and proliferation on, the composite scaffolds. hMSC proliferation was highest in the 30 and 40 wt.% gelatin containing composites. Our experimental data suggested that PCL-gelatin composite nanofibers containing 30-40 wt.% of gelatin and electrospun in diluted acetic acid-ethyl acetate mixture produced nanofiber scaffolds with optimum hydrophilicity, degradability, and bio-functionality for stem cell-based bone tissue engineering.

Costus speciosus is a medicinal plant commonly known as wild ginger distributed in South and Southeast Asian countries. Leaves of this plant are used for ayurvedic treatment regimes in malignancies and mental illness. Rhizome extract from the plant is used to treat malignancies, pneumonia, urinary disorders, jaundice, rheumatism, and diabetes. The goal of this study was to investigate the effects of methanol extract of leaves of C. speciosus on the growth of human hepatocellular carcinoma (HepG2) cells and understand possible mechanisms of its action. Viability of HepG2 cells were measured by MTS assay after 24 h and 48 h treatment with extracts of 1, 10, 50, 100, and 200 μg/mL concentrations. Cell cycle analysis and apoptosis were evaluated by flow cytometry and caspase-3 induction. HepG2 cells treated with 100 μg/mL methanol leaf extract for 24 h displayed a significant reduction in cell viability (P ≤ 0.05). The methanol extract perturbed cell cycle progression, modulated cell cycle and regulated, signal molecules were involved in induction of apoptosis in HepG2 cells. Our findings indicate that phytochemicals of leaves of C. speciosus shows potential for natural therapeutic product development for hepatocellular carcinoma. This is the first report to demonstrate in vitro anticancer activity of leaf extract of C. speciosus in relation to liver cancer.

Metformin, a biguanide, is a commonly administered drug for the management of type 2 diabetes mellitus. The drug received tremendous recognition, when retrospective studies proved metformin-associated reduction in cancer risk. Metformin has potential anticancer effects and an ability to suppress tumor growth both in vitro and in vivo. Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin. Nanotechnology approaches have also been adopted for metformin delivery to cancer cells. This review directs on the application of metformin for the therapy of various cancers and also the different pathways responsible for the metformin derived anticancer effect. It also focuses on the pharmacological applications of metformin and the nanotechnology approaches for metformin delivery.

Recent advancements in cancer nanotechnology have facilitated a better way to diagnosis and provide therapy for prostate cancer. Nanotechnology has the potential to battle tumors at the site, where the cancer begins. There is a need to improve the therapeutic availabilities and the effectiveness of conventional chemotherapeutic agents for prostate cancer. Many therapeutic NPs have been developed with nanotechnology that can specifically target and deliver variety of agents including chemo drugs to destruct the prostate cancer cells without causing any damage to the healthy cells. Theranostic NPs have been developed to specifically target the prostate cancer cells using targeting ligands and to release the anticancer agents in a controlled and time-dependent manner for cancer therapy in combination with assisted imaging to monitor the effectiveness of the therapy in real time. The natural products and surface-modified polymers and metallic NPs have evolved as promising nanomaterials for targeted prostate cancer treatment. This review focuses on the role of alternative medicine, polymeric and metallic and metal oxide NPs in prostate cancer theranostics.

This work explains the fabrication and potential applicability of high thick three dimensional (3-D) electrospun multiscale fibrous scaffolds in tissue engineering by focusing on the possible fabrication techniques. Multiscale fibrous scaffold of poly(lactic acid) (PLA) was fabricated by combining nano and micro fibers in optimum concentrations. Finely chopped multiscale fibers were allowed to undergo compression, freeze-drying, resin embedding, cryo-grinding and layering techniques to make 3D scaffolds and the layer-by-layer method was found to be most suitable for 3-D scaffold fabrication. Cell studies in layered 3D scaffolds were performed using MG 63 cells and infiltration was observed using SEM and confocal microscope. Since the layered high thick 3D scaffold perfectly complies with the requirements, this could be proposed as one of the suitable methods for constructing 3D scaffolds for tissue engineering applications.

Alveolar bone loss and bone defects are the commonly encountered periodontal problems. Large defects do not heal spontaneously and thus require surgical interventions with bone substitutes. Bone grafts have the disadvantages of eliciting an immunologic response with subsequent graft rejection. The success rate of Guided Tissue Regeneration (GTR) is variable because of high susceptibility to infection. Thus emerged the important role of synthetic biomaterials and hence for this purpose we developed a nanocomposite scaffold, using alpha- and beta-chitin hydrogel with bioactive glass ceramic nanoparticles (nBGC) and silver nanoparticles (nAg) by lyophilization technique (aalpha and beta-chitin hydrogel/nBGC/nAg nanocomposite scaffold). The prepared nanoparticles and nanocomposite scaffolds were characterized. In addition, the porosity, swelling, mechanical properties, antibacterial activity, in vitro degradation and biomineralization, cell viability, cell attachment and cell proliferation ability of the prepared composite scaffolds were also evaluated. The results showed that alpha- and beta-chitin/nBGC/nAg composite scaffolds were porous and have the capacity to absorb fluids and swell. The composite scaffolds also showed enhanced antibacterial activity, bioactivity and controlled degradation in comparison to the control scaffolds. Cell viability studies proved the non-toxic nature of the nanocomposite scaffolds. Cell attachment and cell proliferation studies revealed the attachment and spreading nature of cells. All these studies revealed that, these antibacterial nanocomposite scaffolds could be a promising approach for the management of periodontal defects.

A polypyrrole based conducting scaffold was developed by incorporating polypyrrole-alginate (PPy-Alg) blend with chitosan using lyophilization technique and employed this composite as a substrate for bone tissue engineering. PPy-Alg blend was developed by oxidative chemical synthesis of polypyrrole using FeCl3 as oxidizing agent and characterized. The physiochemical characterization of the scaffold was done using SEM, FT-IR along with porosity measurement, swelling and in vitro degradation studies. Surface conductivity of the scaffolds was analyzed using Scanning Electrochemical microscopy (SECM). Results from cell viability and cell proliferation with MG-63 cells using Alamar blue assay confirmed the cytocompatible nature of the developed scaffold. In vitro biomineralization ability of the scaffold was assessed and thus the effectiveness of PPy-Alg/chitosan scaffold in the field of tissue engineering was evaluated., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The increasing interest in using chitosan nanoparticles for controlled drug delivery is hampered by its blood incompatibility, especially for intravenous applications. This study investigated the effects of processing solvents (acetic acid/lactic acid), dispersing media (acidic medium/saline), and surface modifiers (polyethylene glycol, polyvinyl alcohol, and ethylenediaminetetraacetatic acid) on the hemocompatibility of chitosan. Blood compatibility of chitosan nanoparticles prepared by ionotropic gelation with altered surface chemistry was evaluated by assessing their hemolytic activity, platelet aggregation, coagulation, and cytokine induction. It was observed that nanoparticles prepared in lactic acid and dispersed in saline did not show hemolysis, platelet aggregation, or coagulation, whereas nanoparticles prepared in acetic acid showed strong hemolysis. Surface modifiers were not observed to significantly affect blood compatibility, with the exception of EDTA, which delayed blood clotting times. Thus, chitosan nanoparticles prepared in lactic acid and dispersed in saline may be an ideal nanocarrier for parenteral applications., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.)

The present study provides the first report on the preparation and utilization of camphoric carbon nanobeads grafted onto Ni/NiO nanowires for rechargeable electrodes for energy-storage applications. These functionally graded nanowires were electrophoretically deposited onto nickel foils and processed into high-surface-area electrodes. A detailed study has been performed to elucidate the effect of carbon content, different electrolytes, and their concentrations on these nanowires. BET surface area analysis revealed that these grafted nanowires could exhibit a high surface area of about 106 m 2  g -1 , compared with pristine nanowires, which exhibited a surface area of about 45 m 2  g -1 . From the analysis of relevant electrochemical parameters, an intrinsic correlation between the capacitance, internal resistance, and the surface morphology has been deduced. Relative contributions of capacitive and diffusion-controlled processes underlying these thin-film electrodes have been mathematically modeled. These thin-film electrodes exhibited specific mass capacitance values as high as (1950±80) and (1140±60) F g -1 , as determined from cyclic voltammetry and charge discharge curves, respectively; these values were 30-50 % higher than that of a pristine nanowire electrode. Furthermore, a working model button cell employing these rechargeable electrodes is also described, which exhibited energy and power densities of 83 and 75 Wh kg -1 , respectively. This study shows that electrodes based on such nanowire/carbon nanobead configurations can allow significant room for improvement in energy density, power density, and cyclic stability of supercapacitor/battery systems., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The study aims at the targeted imaging using CdTe/ZnTe core shell QDs and delivery of paclitaxel (PTX) loaded fibrinogen coated yellow-QDs (PTX-fib-yellow-QDs) towards breast cancer cells via the alpha5Beta1-integrins. We developed fibrinogen coated different sized CdTe/ZnTe core shell quantum dots of 2-10 nm size, which have been prepared by one-pot aqueous-phase approach. The fib-coated-QDs (fib-coated-QDs) and PTX-fib-yellow-QDs were prepared by two-step coacervation technique using CaCl2 as cross-linker. Particle size of fib-coated-QDs was in between 60-220 nm while PTX-fib-yellow-QDs showed 180 +/- 40 nm. The MTT assay confirmed cytocompatibility of fib-coated-QDs on L929 and MCF-7 than bare QDs, whereas significant toxicity toward MCF-7 by PTX-fib-yellow-QDs was observed. The hemocompatible fib-coated-QDs showed enhanced localization and retention toward alpha5beta1-integrins +ve MCF-7 compared to alpha5beta1-integrins -ve L929 cells. The specific binding of fib-coated-yellow-QDs was further confirmed with alpha5beta1-integrins +ve HeLa and alpha5/beta1-integrins -ve HT29 cells. Cellular uptake studies revealed localization of PTX-fib-coated-yellow-QDs inside MCF-7 cells compared to the normal L929 cells. These results indicated that fib-coated-QDs could be used for targeted imaging and as a suitable "nanocarrier" aiming breast cancer cells.

Poor bioavailability of antifungal drugs due to the various protective mechanisms of the eye is a serious concern for the treatment of corneal fungal infections in today's world. The use of nanosystems that can improve the bioavailability of these antifungal drugs is relatively a new idea being conceived and here we have synthesized fluconazole loaded chitin nanogels (Flu-CNGs) which can be used for the treatment of corneal fungal infections. These nanogels were characterized using DLS, Zeta potential, SEM, FTIR and TG/DTA. The prepared Flu-CNGs have controlled release pattern which is ideal for the continuous availability of fluconazole over a longer period of time for an effective fungal treatment. Flu-CNGs are haemocompatible, cytocompatible and also showed very good cell uptake in human dermal fibroblast cells and penetration to the deeper sections of the porcine cornea with no signs of destruction or inflammation to corneal cells as shown in ex vivo permeation studies.

Combination of three imaging techniques such as nuclear, magnetic and near-infrared fluorescence can aid in improved diagnosis of disease by synergizing specific advantages of each of these techniques such as deep tissue penetration of radiation signals, anatomical and functional details provided by magnetic contrast and better spatial resolution of optical signals. In the present work, we report the development of a multimodal contrast agent based on calcium phosphate nanoparticles (nCP), doped with both indocyanine green (ICG) and Gadolinium (Gd(3+)), and labeled with 99m-Technetium-methylene diphosphonate ((99m)Tc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd(3+) and (99m)Tc were optimized at ∼0.15wt%, 3.38at% and ∼0.002ng/mg of nCP, respectively. The leaching-out of ICG was protected by an additional coating of polyethyleneimine (PEI). Toxicological evaluation of the final construct carried out on healthy human mononuclear cells, red-blood cells and platelets, showed excellent hemocompatibility. In vivo multimodal imaging using mice models revealed the ability to provide near-infrared, magnetic and nuclear contrast simultaneously. The nanoparticles also showed the potential for improved MR based angio-imaging of liver. Retention of intravenously administrated nanoparticles in the liver was reduced with PEGylation and the clearance was observed within 48h without causing any major histological changes in vital organs. Thus, we developed a non-toxic tri-modal nano-contrast agent using calcium phosphate nanoparticles and demonstrated its potential for combined nuclear, magnetic and near-infrared imaging in vivo., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This work explains about the development of a unique tubular scaffold for vascular tissue engineering. The inner layer/layers was made up of aligned poly (lactic acid) (PLA) nano fibers and outer layers were composed of random multiscale fibers of poly(caprolactone) (PCL)/PLA providing larger pores for Smooth Muscle Cell (SMC) penetration. The fabricated scaffolds were characterized by SEM. Cell attachment and infiltration studies using SMCs on the multiscale fibers were characterized by SEM and confocal microscopy. Blood compatibility of the scaffold was analysed by haemolysis-coagulation assays, platelet activation studies and the effect of material/fiber alignment on the morphological stability of Red Blood Cells (RBCs) were evaluated using SEM. Since this hierarchically designed tubular scaffold closely mimics the morphology of native vessel, this could be a better candidate for vascular tissue engineering.

In this work, the attachment, viability and functionality of rat Blood Outgrowth Endothelial Cells (rBOEC) and genetically modified rBOEC (rBOEC/eNOS-GFP), which over express endothelial nitric oxide synthase (eNOS), were investigated on Poly(lactic acid) (PLA)-chitosan and PLA-chitosan-collagen nanofibrous scaffolds. Both the cell types displayed good attachment, remained viable and functional on both scaffolds. Moreover, incorporation of collagen in the scaffold helped in sustaining the rBOEC for upto one week, although collagen was not found necessary for rBOEC/eNOS-GFP. We conclude that PLA-chitosan based nanofibrous scaffolds can be a potential candidate for BOEC based wound healing applications., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Environmental contamination by metals is a serious threat to the biological sustainability of coastal ecosystems. Our current understanding of the potential biological effects of metals in these ecosystems is limited. This study tested the transcriptional expression of immune- and stress-response genes in Sydney Rock oysters (Saccostrea glomerata). Oysters were exposed to four metals (cadmium, copper, lead and zinc) commonly associated with anthropogenic pollution in coastal waterways. Seven target genes (superoxide dismutase, ferritin, ficolin, defensin, HSP70, HSP90 and metallothionein) were selected. Quantitative (real-time) PCR analyses of the transcript expression of these genes showed that each of the different metals elicited unique transcriptional profiles. Significant changes in transcription were found for 18 of the 28 combinations tested (4 metals × 7 genes). Of these, 16 reflected down-regulation of gene transcription. HSP90 was the only gene significantly up-regulated by metal contamination (cadmium and zinc only), while defensin expression was significantly down-regulated by exposure to all four metals. This inhibition could have a significant negative effect on the oyster immune system, promoting susceptibility to opportunistic infections and disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ovarian cancer is the ninth most common cancer amongst women and ranked as fifth in terms of the cause of cancer related mortality accounting for more deaths than any other cancer of the female reproductive system. Gemcitabine is the most common chemotherapeutic agent used in the treatment of ovarian cancer despite of its disadvantage of having a very lesser half life. In this study, we have envisaged the use of a highly porous, biomimetic and implantable pectin scaffold embedded with gemcitabine loaded fibrin nanoconstructs to improve the half life of the drug, thereby providing localized therapy for ovarian cancer. The controlled and sustained release of the chemokine from the scaffold system was extensively analyzed in vitro different pH environments. The composite scaffolds were found to be highly biocompatible when tested with mammalian cell lines. The excellent cytotoxicity and apoptosis responses induced in ovarian cancer, PA- 1 cell lines proved that the nanocomposite Pectin scaffolds loaded with specific chemokine can be used as implantable "therapeutic wafers" for distracting metastatic cancer cells and thus improve the survival rate of ovarian cancer afflicted individuals.

The purple sea urchin has a complex immune system that is likely mediated by gene expression in coelomocytes (blood cells). A broad array of potential immune receptors and immune response proteins has been deduced from their gene models. Here we use shotgun mass spectrometry to describe 307 proteins with possible immune function in sea urchins including proteins involved in the complement pathway and numerous SRCRs. The relative abundance of dual oxidase 1, ceruloplasmin, ferritin and transferrin suggests the production of reactive oxygen species in coelomocytes and the sequestration of iron. Proteins such as selectin, cadherin, talin, galectin, amassin and the Von Willebrand factor may be involved in generating a strong clotting reaction. Cell signaling proteins include a guanine nucleotide binding protein, the Rho GDP dissociation factor, calcium storage molecules and a variety of lipoproteins. However, based on this dataset, the expression of TLRs, NLRs and fibrinogen domain containing proteins in coelomic fluid and coelomocytes could not be verified., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The characterization and classification of smokeless tobacco products has been a continuously evolving process. This is based on a number of different parameters like nicotine content, moisture content, amount of heavy metals, pH, and in vitro cytotoxicity assays. Their contexts often vary between countries, research institutions, and legal requirements. The categorisation of these products is quite challenging due to the diffused sample sizes, diverse array of branded products on offer, and the absence of a centralized manufacturing facility. This study aims at a systematic classification of 10 smokeless tobacco product samples from the retail market based on their potential toxicity upon long-term use. The estimation of potential toxicity follows a well-established method that employs the concentration of toxic metals in the different samples. The potential toxicity as well as heavy metal concentrations of the smokeless tobacco products analysed was found to be much higher than acceptable limits. For instance, the levels of lead, cadmium, copper and zinc of 2.5, 1, 4 and 23 ppm, respectively, are well above their recommended limits. The results from the study indicate that chronic use of smokeless tobacco products is a significant health risk, especially in the vulnerable population. Further studies of this nature will help establish a toxicological fingerprint on the diverse class of products that floods the market now.

Fabricating scaffolds mimicking the native extracellular matrix (ECM) in both structure and function is a key challenge in the field of tissue engineering. Previously we have demonstrated a novel electrospinnig method for the fabrication of fibrin nanofibers using Poly(vinyl alcohol) (PVA) as an 'electrospinning-driving' polymer. Here we demonstrate the fabrication and characterization of a multiscale fibrin based composite scaffold with polycaprolactone (PCL) by sequential electrospinning of PCL microfibers and fibrin nanofibers. This multiscale scaffold has great potential for tissue engineering applications due to the combined benefits of biological nanofibers such as cell attachment and proliferation and that of microfibers such as open structure, larger pore size and adequate mechanical strength. Physico chemical characterization of the electrospun scaffold was done by Scanning Electron Microscopy (SEM), Contact angle analysis, fibrin specific Phosphotungstic acid haematoxyllin (PTAH) staining and evaluation of mechanical properties. SEM data revealed the formation of bead free nanofibers of fibrin with a fiber diameter ranging from 50-500 nm and microfibers of PCL in the size range of 1 microns to 2.5 microns. These dimensions mimic the hierarchical structure of ECM found in native tissues. Cell attachment and viability studies using human mesenchymal stem cells (hMSC) revealed that the scaffold is non toxic and supports cell attachment, spreading and proliferation. In addition, we examined the inflammatory potential of the scaffold to demonstrate its usefulness in tissue engineering applications.

Nanoparticle mediated delivery of antineoplastic agents, functionalized with monoclonal antibodies has achieved extraordinary potential in cancer therapy. The objective of this study was to develop a drug delivery system comprising O-carboxymethyl chitosan (O-CMC) nanoparticles, surface-conjugated with Cetuximab (Cet) for targeted delivery of paclitaxel (PTXL) to Epidermal Growth Factor Receptor (EGFR) over-expressing cancer cells. Nanoparticles around 180±35nm and negatively charged were prepared through simple ionic gelation technique. The alamar blue assay indicated that these targeted nanoparticles displayed a superior anticancer activity compared to non-targeted nanoparticles. The nanoformulation triggered enhanced cell death (confirmed by flow cytometry) due to its higher cellular uptake. The selective uptake of Cet-PTXL-O-CMC nanoparticles by EGFR +VE cancer cells (A549, A431 and SKBR3) compared to EGFR -VE MIAPaCa-2 cells confirms the active targeting and delivery of PTXL via the targeted nanomedicine. Cet-PTXL-O-CMC nanoparticles can be used a promising candidate for the targeted therapy of EGFR over expressing cancers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150±50 nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200±50 nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery., (Copyright © 2012 Elsevier B.V. All rights reserved.)

An injectable composite gel was developed from alginic and hyaluronic acid. The enzymatically cross-linked injectable gels were prepared via the oxidative coupling of tyramine modified sodium algiante and sodium hyaluronate in the presence of horse radish peroxidase (HRP) and hydrogen peroxide (H2O2). The composite gels were prepared by mixing equal parts of the two tyraminated polymer solutions in 10U HRP and treating with 1.0% H2O2. The properties of the alginate gels were significantly affected by the addition of hyaluronic acid. The percentage water absorption and storage modulus of the composite gels were found to be lower than the alginate gels. The alginate and composite gels showed lower protein release compared to hyaluronate gels in the absence of hyaluronidase. Even hyaluronate gels showed only approximately 10% protein release after 14 days incubation in phosphate buffer solution. ATDC-5 cells encapsulated in the injectable gels showed high cell viability. The composite gels showed the presence of enlarged spherical cells with significantly higher metabolic activity compared to cells in hyaluronic and alginic acid gels. The results suggest the potential of the composite approach to develop covalently cross-linked hydrogels with tuneable physical, mechanical, and biological properties., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Myocardial tissue engineering is one of the most promising treatment strategies to restore heart function after a massive heart attack. The biomaterials, cells, and scaffold design play important roles in engineering of heart tissue. In this study, we have developed a fibrin-based multiscale electrospun composite scaffold for myocardial regeneration. Fibrin is the natural wound-healing matrix having angiogenic potential and comprehensively used for tissue engineering applications. It provides a natural environment for cell attachment, migration, and proliferation. Morphological, chemical, and mechanical characterization of the scaffolds was done by scanning electron microscopy, fibrin-specific phosphotungstic acid hematoxylin staining, and mechanical testing. The fiber diameters of fibrin nanofibers range from 50 to 300 nm and that of poly (lactide-co-glycolide) microfibers range from 2 to 4 μm, which mimics the structural hierarchy of native myocardial tissue. Our results indicate that this scaffold enhances the differentiation of mesenchymal stem cells into cardiomyocytes. The cardiac phenotype of the cells was confirmed by the presence of cardiac-specific proteins like α-sarcomeric actinin, troponin, tropomyosin, desmin, and atrial natriuretic peptide Estimation of D-Dimer in the culture supernatant for 2 weeks and analysis of scaffold for 3 weeks of in vitro culture of cardiomyocytes indicated the degradation of fibrin and presence of newly synthesized collagen respectively. Our results demonstrate the promising potential of this scaffold for myocardial tissue engineering applications.

Targeted biological contrast agents are emerging as promising candidates in the field of cancer theragnostics. Herein, we report an ambient temperature synthesis of a nanosized, antibody functionalized lanthanide doped CaF 2 biolabel and demonstrate in vitro its potential for cancer cell targeting efficacy and specificity. Monodispersed citrate stabilized lanthanide (Eu 3+ ) doped CaF 2 nanoparticles with size ∼25 nm, exhibiting strong fluorescent emission at 612 nm, were prepared using an aqueous wet chemical route at room temperature. Biofunctionalization of the fluorescent nanoparticles using an anti-EGFR antibody through EDC-NHS coupling chemistry enabled targeting of EGFR over-expressing cells. The nanobioconjugates showed preferential binding to EGFR +ve oral epithelial carcinoma cells (KB) and human epidermoid carcinoma cells (A431) with no accumulation onto EGFR -ve non-cancerous NIH 3T3 cells. The fluorescence was maintained after the bioconjugation as well as after attachment to the cancer cells, demonstrating their potential as targeted biolabels. Cytotoxicity evaluation with several cancerous (A431, KB) and non-cancerous (NIH 3T3, L929) cell lines revealed no toxicity at concentrations up to 1 mM. Thus, the fluorescence characteristics and biocompatibility, coupled with the molecular receptor targeting capability, suggest the potential use of CaF 2 in the field of bioimaging.

A biomimetic scaffold which can very closely mimic the extracellular matrix of the bone was fabricated by incorporating nano-bioceramic particles such as nano bioglass (nBG) and nano hydroxyapatite (nHAp) within electrospun nanofibrous scaffold. A comparative study between nHAp incorporated poly(caprolactone) (PCL)-chitosan (CS) and nBG incorporated PCL-CS nanofibrous scaffolds was carried out and their feasibility in tissue engineering was investigated. All the samples were optimized to obtain fibers of similar diameter from 100-200 nm for the ease of comparison between the samples. Protein adsorption studies showed that PCL-CS incorporated with 3 wt% nHAp and 3 wt% nBG adsorbed more proteins on their surface than other samples. Cell attachment and proliferation studies using human periodontal ligament fibroblast cells (hPLFs) and osteoblast like cells (MG-63 cell lines) showed that nBG incorporated samples are slightly superior to nHAp incorporated counterparts. Cell viability test using alamar blue assay and live/dead staining confirms that the scaffolds are cytocompatible. ALP activity confirmed the osteoblastic behavior of hPDLFs. Also the presence of nHAp and nBG enhanced the ALP activity of hPDLF on the PCH3 and PCB3 scaffolds. These studies indicate that nBG incorporated electrospun scaffolds are comparatively better candidates for orthopedic and periodontal tissue engineering applications.

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using chitosan (CS) and dextran sulphate (DS) nanoparticles and were characterized using different techniques. The prepared nanoparticles showed a size of 80-120 nm with an entrapment efficiency of 55 +/- 6.95%. In addition, blood compatibility, in vitro cytotoxicity, drug release and cellular uptake studies were also carried out. The drug release studies showed a sustained and pH dependent release pattern as a result, after 120 h about 66% drug release occurred at pH 7.4 and 78% release occurred in acidic pH. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) experiments proved the preferential toxicity of drug loaded nanoparticles towards prostate cancer cells (PC3) unlike in normal cells, mouse fibroblast cells (L929). The cell death mechanism of drug loaded nanoparticles for a concentration of 50 and 75 nM showed 28 +/- 2 and 35.2 +/- 4% apoptosis in samples treated with the PC3 cells after 24 h. Fluorescent microscopic imaging and flow cytometry confirmed the preferential uptake of the nanoparticles (NPs) in the prostate cancer cells (PC3) unlike in normal (L929) cells. Hence the developed FLT loaded CS-DS NPs could be used as a promising system for controlled delivery in prostate cancer.

In this work chitosan-hyaluronan composite sponge incorporated with chondroitin sulfate nanoparticle (nCS) was developed. The fabrication of hydrogel was based on simple ionic cross-linking using EDC, followed by lyophilization to obtain the composite sponge. nCS suspension was characterized using DLS and SEM and showed a size range of 100-150 nm. The composite sponges were characterized using SEM, FT-IR and TG-DTA. Porosity, swelling, biodegradation, blood clotting and platelet activation of the prepared sponges were also evaluated. Nanocomposites showed a porosity of 67% and showed enhanced swelling and blood clotting ability. Cytocompatibility and cell adhesion studies of the sponges were done using human dermal fibroblast (HDF) cells and the nanocomposite sponges showed more than 90% viability. Nanocomposite sponges also showed enhanced proliferation of HDF cells within two days of study. These results indicated that this nanocomposite sponges would be a potential candidate for wound dressing., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this work, Hemigraphis alternata extract incorporated chitosan scaffold was synthesized and characterized for wound healing. The antibacterial activity of Hemigraphis incorporated chitosan scaffold (HIC) against Escherichia coli and Staphylococcus aureus was evaluated which showed a reduction in total colony forming units by 45-folds toward E. coli and 25-fold against S. aureus respectively. Cell viability studies using Human Dermal Fibroblast cells (HDF) showed 90% viability even at 48 h when compared to the chitosan control. The herbal scaffold made from chitosan was highly haemostatic and antibacterial. The obtained results were in support that the herbal scaffold can be effectively applied for infectious wounds., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Recently, scaffolds for tissue regeneration purposes have been observed to utilize nanoscale features in an effort to reap the cellular benefits of scaffold features resembling extracellular matrix (ECM) components. However, one complication surrounding electrospun nanofibers is limited cellular infiltration. One method to ameliorate this negative effect is by incorporating nanofibers into microfibrous scaffolds. This study shows that it is feasible to fabricate electrospun scaffolds containing two differently scaled fibers interspersed evenly throughout the entire construct as well as scaffolds containing fibers composed of two discrete materials, specifically fibrin and poly(ε-caprolactone). In order to accomplish this, multiscale fibrous scaffolds of different compositions were generated using a dual extrusion electrospinning setup with a rotating mandrel. These scaffolds were then characterized for fiber diameter, porosity and pore size and seeded with human mesenchymal stem cells to assess the influence of scaffold architecture and composition on cellular responses as determined by cellularity, histology and glycosaminoglycan (GAG) content. Analysis revealed that nanofibers within a microfiber mesh function to maintain scaffold cellularity under serum-free conditions as well as aid the deposition of GAGs. This supports the hypothesis that scaffolds with constituents more closely resembling native ECM components may be beneficial for cartilage regeneration.

Purpose: β-chitin hydrogel/nZnO composite bandage was fabricated and evaluated in detail as an alternative to existing bandages., Methods: β-chitin hydrogel was synthesized by dissolving β-chitin powder in Methanol/CaCl(2) solvent, followed by the addition of distilled water. ZnO nanoparticles were added to the β-chitin hydrogel and stirred for homogenized distribution. The resultant slurry was frozen at 0°C for 12 h. The frozen samples were lyophilized for 24 h to obtain porous composite bandages., Results: The bandages showed controlled swelling and degradation. The composite bandages showed blood clotting ability as well as platelet activation, which was higher when compared to the control. The antibacterial activity of the bandages were proven against Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli). Cytocompatibility of the composite bandages were assessed using human dermal fibroblast cells (HDF) and these cells on the composite bandages were viable similar to the Kaltostat control bandages and bare β-chitin hydrogel based bandages. The viability was reduced to 50-60% in bandages with higher concentration of zinc oxide nanoparticles (nZnO) and showed 80-90% viability with lower concentration of nZnO. In vivo evaluation in Sprague Dawley rats (S.D. rats) showed faster healing and higher collagen deposition ability of composite bandages when compared to the control., Conclusions: The prepared bandages can be used on various types of infected wounds with large volume of exudates.

In this work, we have developed chitosan hydrogel/nanofibrin composite bandages (CFBs) and characterized using Fourier transform-infrared spectroscopy and scanning electron microscopy. The homogeneous distribution of nanofibrin in the prepared chitosan hydrogel matrix was confirmed by phosphotungstic acid-hematoxylin staining. The mechanical strength, swelling, biodegradation, porosity, whole-blood clotting, and platelet activation studies were carried out. In addition, the cell viability, cell attachment, and infiltration of the prepared CFBs were evaluated using human umbilical vein endothelial cells (HUVECs) and human dermal fibroblast (HDF) cells. It was found that the CFBs were microporous, flexible, biodegradable, and showed enhanced blood clotting and platelet activity compared to the one without nanofibrin. The prepared CFBs were capable of absorbing fluid and this was confirmed when immersed in phosphate buffered saline. Cell viability studies on HUVECs and HDF cells proved the nontoxic nature of the CFBs. Cell attachment and infiltration studies showed that the cells were found attached and proliferated on the CFBs. In vivo experiments were carried out in Sprague-Dawley rats and found that the wound healing occurred within 2 weeks when treated with CFBs than compared to the bare wound and wound treated with Kaltostat. The deposition of collagen was found to be more on CFB-treated wounds compared to the control. The above results proved the use of these CFBs as an ideal candidate for skin tissue regeneration and wound healing.

This study focuses on development and evaluation of 5-fluorouracil (5-FU) loaded chitin nanogels (FCNGs). It formed good, stable aqueous dispersion with spherical particles in 120-140 nm size range and showed pH responsive swelling and drug release. The FCNGs showed toxicity on melanoma (A375) in a concentration range of 0.4-2.0mg/mL, but less toxicity toward human dermal fibroblast (HDF) cells by MTT assay. Confocal analysis revealed uptake of FCNGs by both cells. From skin permeation experiments, FCNGs showed almost same steady state flux as that of control 5-FU but the retention in the deeper layers of skin was found to be 4-5 times more from FCNGs. Histopathological evaluation revealed loosening of the horny layer of epidermis by interaction of cationically charged chitin, with no observed signs of inflammation and so FCNGs can be a good option for treatment of skin cancers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Nanogels are nanosized hydrogel particles formed by physical or chemical cross-linked polymer networks. The advantageous properties of nanogels related to the ability of retaining considerable amount of water, the biocompatibility of the polymers used, the ability to encapsulate and protect a large quantity of payload drugs within the nanogel matrix, the high stability in aqueous media, their stimuli responsively behavior potential, and the versatility in release drugs in a controlled manner make them very attractive for use in the area of drug delivery. The materials used for the preparation of nanogels ranged from natural polymers like ovalbumin, pullulan, hyaluronic acid, methacrylated chondroitin sulfate and chitosan, to synthetic polymers like poly (N-isopropylacrylamide), poly (Nisopropylacrylamide- co-acrylic acid) and poly (ethylene glycol)-b-poly (methacrylic acid). The porous nanogels have been finding application as anti-cancer drug and imaging agent reservoirs. Smart nanogels responding to external stimuli such as temperature, pH etc can be designed for diverse therapeutic and diagnostic applications. The nanogels have also been surface functionalized with specific ligands aiding in targeted drug delivery. This review focus on stimuli-sensitive, multi-responsive, magnetic and targeted nanogels providing a brief insight on the application of nanogels in cancer drug delivery and imaging in detail.

Research into marsupial adaptive immunity during ontogeny has been hampered by the lack of antibodies that react to marsupial immunological cell populations. In this study, newly synthesised polyclonal antibodies to the T cell marker, CD8, have been developed and used to investigate the ontogeny and distribution of this T cell population in the tammar wallaby. Immunohistochemical analysis indicated that the distribution of the CD8 lymphocytes in the lymphoid tissues of tammar neonates during the first 144 days of pouch life was similar to that of the eutherian mammals. However, CD8α(+) lymphocytes were observed in the intestines of tammar neonates prior to their first appearance in the cervical thymus, an observation that has not been found in eutherians. A dual labelling immunohistochemical approach was used for the indirect demonstration of CD4 and enabled the simultaneous detection in the tammar wallaby tissues of the two major T-lymphocyte populations, CD4 and CD8 that are associated with adaptive immunity. As in eutherian mammals, CD4(+) cells were the predominant T cell lymphocyte subset observed in the spleen while in the nodal tissues, an age-related decrease in the CD4(+)/CD8(+) ratio was noted. These antibodies provide a new immunological tool to study the role of T cell subsets in marsupial immunity and disease pathogenesis studies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We developed chitin hydrogel/nano ZnO composite bandages using chitin hydrogel and ZnO nanoparticles (nZnO). The homogenized mixture of chitin hydrogel and nZnO was freeze-dried to obtain micro-porous composite bandages. The prepared nanocomposite bandages were characterized using FT-IR, XRD and SEM. In addition, blood clotting, antibacterial, swelling, cytocompatibility and cell attachment capability of the prepared nanocomposite bandages were evaluated. The nanocomposite bandages showed enhanced swelling, blood clotting and antibacterial activity. The incorporation of nZnO helped to attain antibacterial activity. Cytocompatibility studies were carried out using human dermal fibroblast (HDF) cells proved the non-toxic nature of the composite bandages. HDF cell attachment and infiltration analysis showed that the cells were attached and penetrated into the interior (250 microm) of the nanocomposite bandages. These studies revealed that, this nanocomposite can be used for burn, diabetic and chronic wound defects.

Nanofibrous semi-synthetic polymeric nanocomposite scaffolds were engineered by incorporating a maximum of 15 wt% biopolymeric gelatin nanoparticles (nGs) into the synthetic polymer poly(ε-caprolactone) (PCL) prior to electrospinning. The effect of nGs in altering the physico-chemical properties, cell material interaction and biodegradability of the scaffolds was evaluated. Experimental results showed that the inherent hydrophobicity of PCL scaffolds remained unaltered even after the incorporation of hydrophilic nGs. However, breakdown of the continuous nanofibers into lengths less than 7 µm occurred within four to eight weeks in the presence of nGs in contrast with the greater than two year time frame for the degradation of PCL fibers alone that is known from the literature. In terms of cell-material interaction, human mesenchymal stem cells (hMSCs) were found to attach and spread better and faster on PCL_nG scaffolds compared to PCL scaffolds. However, there was no difference in hMSC proliferation and differentiation into osteogenic lineage between the scaffolds. These results indicate that PCL_nG nanofibrous nanocomposite scaffolds are an improvement over PCL scaffolds for bone tissue engineering applications in that the PCL_nG scaffolds provide improved cell interaction and are able to degrade and resorb more efficiently.

Synthesis of biocompatible gold nanoparticles having tunable optical absorbance finds immense use in biomedical applications such as cancer diagnosis and photothermal therapy. Hence, it is imperative to develop environment and bio-friendly green chemical processes that aid in preparing gold nanoparticles with tunable optical properties. In the present work, phytochemicals present in the medicinal herb, viz., garlic, were used to provide the dual effects of reduction of gold salts to gold nanoparticles as well as stabilization, in a single step process. The optical tunability of nanogold with respect to concentration of precursor and volume of garlic extract, processing conditions of garlic, its differing molecular weight fractions, reaction time and temperature has been demonstrated. The presence of a range of anisotropic nanogold including nanotriangles, nanorods and nanospheres as evident from TEM endows the colloid with a tunable optical absorption, specifically into the near infrared region. In vitro stability studies of the colloidal suspension in various media including saline, BSA, histidine and PBS showed that gold nanoparticles did not aggregate with time or differing pH conditions. The role of the garlic phytochemicals in providing stability against agglomeration was also substantiated by FTIR studies. Cytotoxicity studies performed using spherical and anisotropic gold nanoparticles on MCF-7 and L929 cell lines proved the biocompatibility of the material up to high doses of 500 microg/ml. The present work highlights the role of garlic phytochemicals in preparing biocompatible metallic gold nanoparticles with tunable optical properties and good in vitro stability, suggesting its potential use for molecular imaging or therapeutic nanomedicines.

Intracellular bacterial infections are recurrent, persistent and are difficult to treat because of poor penetration and limited availability of antibiotics within macrophages and epithelial cells. We developed biocompatible, 200 nm sized tetracycline encapsulated O-carboxymethyl chitosan nanoparticles (Tet-O-CMC Nps) via ionic gelation for its sustained delivery of Tet into cells. S. aureus binds and aggregates with Tet-O-CMC Nps increasing drug concentrations at the infection site. Tet-O-CMC Nps were sixfold more effective in killing intracellular S. aureus compared to Tet alone in HEK-293 and differentiated THP1 macrophage cells proving it to be an efficient nanomedicine to treat intracellular S. aureus infections., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This study used proteomics to assess the impacts of metal contamination in the field on Sydney Rock oysters. Oysters were transplanted into Lake Macquarie, NSW, for two weeks in both 2009 and 2010. Two-dimensional electrophoresis identified changes in protein expression profiles of oyster haemolymph between control and metal contaminated sites. There were unique protein expression profiles for each field trial. Principal components analysis attributed these differences in oyster proteomes to the different combinations and concentrations of metals and other environmental variables present during the three field trials. Identification of differentially expressed proteins showed that proteins associated with cytoskeletal activity and stress responses were the most commonly affected biological functions in the Sydney Rock oyster. Overall, the data show that proteomics combined with multivariate analysis has the potential to link the effects of contaminants with biological consequences., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Regeneration of skin after a large area wound or burn is often difficult without the aid of a scaffold. In this work we developed a 3D macroporous chitin/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hydrogel blend by normal solution chemistry and lyophilized it to get the scaffold. The developed scaffold was then characterized and it showed a slow degrading as well as biocompatible nature. The blend hydrogel scaffold showed 67% porosity and the pore size was less than 20 μm. Cytocompatibility of the scaffold was proved by Alamar blue assay using Human Dermal Fibroblast cells (HDF). The blend hydrogel scaffold showed a two fold increase in cell number over control within three days of culture. The chitin/PHBV blend also showed enhanced HDF cell attachment and proliferation. These preliminary results prove its suitability for scaffold based skin tissue regeneration., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Poly(caprolactone) (PCL) has been frequently considered for bone tissue engineering because of its excellent biocompatibility. A drawback, however, of PCL is its inadequate mechanical strength for bone tissue engineering and its inadequate bioactivity to promote bone tissue regeneration from mesenchymal stem cells. To correct this deficiency, this work investigates the addition of nanoparticles of silica (nSiO(2)) to the scaffold to take advantage of the known bioactivity of silica as an osteogenic material and also to improve the mechanical properties through nanoscale reinforcement of the PCL fibers. The nanocomposite scaffolds and the pristine PCL scaffolds were evaluated physicochemically, mechanically, and biologically in the presence of human mesenchymal stem cells (hMSCs). The results indicated that, when the nanoparticles of size approximately 10 nm (concentrations of 0.5% and 1% w/v) were embedded within, or attached to, the PCL nanofibers, there was a substantial increase in scaffold strength, protein adsorption, and osteogenic differentiation of hMSCs. These nSiO(2) nanoparticles, when directly added to the cells evidently pointed to ingestion of these particles by the cells followed by cell death. The polymer nanofibers appeared to protect the cells by preventing ingestion of the silica nanoparticles, while at the same time adequately exposing them on fiber surfaces for their desired bioactivity.

Polycaprolactone (PCL) is a widely accepted synthetic biodegradable polymer for tissue engineering, however its use in hard tissue engineering is limited because of its inadequate mechanical strength and low bioactivity. In this study, we used halloysite nanoclay (NC) as an inorganic filler material to prepare PCL/NC fibrous scaffolds via electrospinning technique after intercalating NC within PCL by solution intercalation method. The obtained nanofibrous mat was found to be mechanically superior to PCL fibrous scaffolds. These scaffolds allowed greater protein adsorption and enhanced mineralization when incubated in simulated body fluid. Moreover, our results indicated that human mesenchymal stem cells (hMSCs) seeded on these scaffolds were viable and could proliferate faster than in PCL scaffolds as confirmed by fluorescence and scanning electron microscopic observations. Further, osteogenic differentiation of hMSCs on nanoclay embedded scaffolds was demonstrated by an increase in alkaline phosphatase activity when compared to PCL scaffold without nanoclay. All of these results suggest the potential of PCL/NC scaffolds for bone tissue engineering.

In this work we developed metformin loaded O-carboxymethyl chitosan (O-CMC) nanoparticles (NPs) by ionic-gelation method. The prepared NPs of 240 ± 50 nm size with spherical morphology exhibited a pH sensitive release of metformin in vitro. Cytotoxicity studies showed that the drug-incorporated NPs induced significant toxicity on pancreatic cancer cells (MiaPaCa-2) compared to normal cells (L929). Metformin loaded NPs exhibited nonspecific internalization by normal and pancreatic cancer cells; however metformin released from the NPs induced preferential toxicity on pancreatic cancer cells. Our preliminary studies suggested that such a novel approach could possibly overcome the current limitations of metformin in its clinical application against pancreatic cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)