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The clinical application of gemcitabine is limited by hydrophilicity and low plasma half-life. Herein, we developed a chitosan-based nanogel to provide controlled release of gemcitabine and relieve...

Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance and cancer relapses. The Notch pathway regulates CSCs, and it is essential for the self-renewal and maintenance of CSCs. Gamma-secretase inhibitor such as DAPT, reduces the CSCs by inhibiting Notch pathway. Apart from its advantages, DAPT causes side effects which making it necessary to use new strategies. Since vitamin C (Ascorbic Acid: AA) receptors are high on CSCs, they are high in AA uptake and can be used in CSCs targeted therapy. Therefore, in this study we functionalized Au nanoparticles (NPs) with DAPT and AA to target CSCs and increase particle uptake by them. Here, we functionalized Au-AA NPs with DAPT as the target agent. The morphological characteristics of Au-AA NPs and Au-AA-DAPT NPs were investigated by the transmission electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, and zeta potential. After NPs-modified synthesis and confirmation of inhibitor stabilization, their effects on MCF-7 cells were determined by MTT assay. Then, the colony formation and self-renewal ability of MCF-7 cells was evaluated by SP cells analysis and Soft agar colony formation assay. The results of this study indicated that conjugation of DAPT with Au-AA NPs increases the inhibitory effect of DAPT on the growth of MCF-7 cells. Also, it has been shown that Au-AA-DAPT NPs significantly inhibits colony formation and depletes CSCs compared to control cells. Our data demonstrate the involvement of the vitamin C receptors in the increased cellular uptake of DAPT by CSCs. Therefore, targeting CSCs with Au-AA-DAPT NPs could be a promising approach for the treatment. For effective delivery of GSI to CSCs we functionalized Au NPs with vitamin C to target SVCTs that are high on CSCs. The Au-AA-DAPT NP is imported to the cell where it suppresses the γ-secretase, which is responsible for Notch signaling activation.

Background and aim Tyrosinase (EC 1.14.18.1) is responsible for enzymatic browning in fruits and vegetables. Its inhibitors may be applied to efficiently treat hyperpigmentation and are widely used in pharmaceutical and cosmetic products, food supplements and insecticides. Previous studies have shown that heterocyclic compounds with an amino group can inhibit tyrosinase activity. The present study aims to evaluate the inhibitory effect of some novel 2,6-diamino-4-chloropyrimidine derivatives (1a-e) and 2,4,6-triaminopyrimidine (2a-e) including bioactive aniline moiety on the activity of the mushroom tyrosinase. Methods In practice, the azo salt was initially synthesized from aniline derivatives and combined subsequently with the 2,4,6-triaminopyrimidine and 2,6-diamino-4 chloropyrimidine followed by crystallization. The structures of resulting compounds were confirmed by FT-IR, 13C NMR, and 1H NMR. The derivatives (0-100 µM) were evaluated for their inhibitory effect on tyrosinase activity using l-3,4-dihydroxyphenylalanine (l-DOPA) as substrate. Results All compounds showed inhibitory effects against the activity of the enzyme. About 23.72-55.08% inhibition was observed in the presence of 30 µM of each compound. The IC50 values of the synthesized compounds were measured, and their inhibition properties were also visualized by zymography. Based on the results, the compounds 1a-e and 2a-e showed moderate inhibitory activities. Notably, pyrimidine derivatives 1a (IC50=24.68) and 1d (IC50=24.45) also exhibited similar inhibitory activities when compared with the positive control, kojic acid (IC50=25.24 µM). Kinetic studies indicated that the type of inhibition was noncompetitive. Conclusion All results suggest that pyrimidine derivatives, especially 1d and 1a, can be considered as safe and efficient tyrosinase inhibitors.

The textile and dye industries produce waste streams with considerable concentrations of heavy metals and complex organic compounds. There are a number of conventional approaches for the removal of these pollutants but they require a significant amount of capital investment and energy. Some of these treatment processes include coagulation/flocculation/precipitation, reverse osmosis, electro-dialysis and ultrafiltration. Most of these processes reduce the contaminant load to environmentally safe levels but in most cases they produce a large volume of low-density toxic sludge. Alternative bioremediation-based treatment systems have slowly been gaining acceptance in the industrial effluent treatment industry in recent years. Natural organisms are used to break down hazardous substances into less toxic or non-toxic substances. This chapter describes the role of conventional treatment processes and the use of microalgae in the breakdown of complex organic compounds and the concentration and removal of heavy metals from the effluent of the textile and dye industries.

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier.

Tyrosinase (EC 1.14.18.1) is a key copper-containing metalloenzyme widely distributed in nature and plays determinant role in melanin biosynthesis. The enzyme manifests two unusual catalytic properties including oxidase and monooxygenase activities. Its inhibitors may be applied to efficiently treat of hyperpigmentation and widely used in pharmaceutical and cosmetic products, as well as food supplements and insecticides. The present study aims to evaluate the inhibitory effects of some novel azo-hydrazone tautomeric dyes (4a-e) including bioactive thiazolidinone moiety on the activity of the mushroom tyrosinase. When L-3,4-dihydroxyphenylalanine (L-Dopa) was used as the substrate for the enzyme, the compounds 4d, 4a, and 4e showed strong inhibitory effects against the activity of the enzyme (61%, 56%, and 49% inhibition in the presence of 60μM of each compound, respectively). The IC50 values of the synthetized compounds were measured and their inhibition properties were also visualized by zymography. According to tyrosinase inhibitory activity, the compounds 4a, 4c, 4d and 4e exhibited strong inhibitory activities with IC50 values of 45.83, 140.25, 37.59, and 42.31μM, respectively, compared to the positive control kojic acid (29.44μM). Kinetic study of 4d compound (as the most potent inhibitor) revealed that the compound acts as a reversible competitive inhibitor of the enzyme with the Ki value of 31.0μM. We also simulated the molecular docking with the compound 4d and the results confirmed that the compound strongly interacts with the mushroom tyrosinase residues. All results totally suggest that thiazolidine derivatives, especially 4d, 4a, and 4e, can be considered as safe and efficient tyrosinase inhibitors. They also have the potential to be used in the correspond fields.

In this study the hemoglobin heme degradation upon interaction with sodium dodecyl sulfate (SDS) was investigated using UV-vis and fluorescence spectroscopy, multivariate curve resolution analysis, and chemiluminescence method. Our results showed that heme degradation occurred during interaction of hemoglobin with SDS producing three fluorescent components. We showed that the hydrogen peroxide, produced during this interaction, caused heme degradation. In addition, the endogenous hydrogen peroxide was more effective in hemoglobin heme degradation compared to exogenously added hydrogen peroxide. The endogenous form of hydrogen peroxide altered oxyHb to aquamethemoglobin and hemi-chrome at low concentration. In contrast, the exogenous hydrogen peroxide lacked this ability under same conditions.

A sensitive immunoassay method was developed for the detection of HBsAg. A chemiluminescence label was prepared based on the co-immobilization of a secondary antibody and luminol on gold nanoparticles. HBsAg was targeted by a primary antibody, immobilized in polystyrene wells and a secondary antibody, co-immobilized on luminol–gold nanoparticles. After the formation of the immune sandwich, the luminescence intensity was recorded in the presence of hydrogen peroxide as an oxidant agent and Au3+ as an efficient catalyst for luminol oxidation. HBsAg was detected in the linear concentration range from 0.12 to 30 ng mL−1 and had the detection limit of 14 pg mL−1. The proposed method has been successfully applied to determine the HBsAg in patient serums. This method has excellent precision, a good detection limit, a wide linear range, a low cost and is user friendly. With these features, the proposed method is suitable for measuring antigen in patient serums.

In the presence of low energy gamma emitter radioisotopes of thallium-201 (201T1) or technetium-99m (99mTc), H2O2 was generated via radiolysis of water. The produced H2O2 was amperometrically determined using an anthraquinone 2-carboxylic acid modified horseradish peroxidase on glassy carbon electrode. In the presence of each radioisotope, the cathodic current produced due to the amperometric detection of H2O2, was designated as biosensor response. At the applied potential of -550 mV (vs. Ag/AgCl), the biosensor showed the sensitivities of 1.937 and 2.278 nA h ώGy-1 towards H2O2 produced by 201Tl and 99mTc respectively. Finally, the calibration curves for dose rate determination of 201Tl and 99mTc have been presented and the correlations between biosensor response to H2O2 and the gamma emitter dose rates for 201Tl and 99mTc are established.

This report describes the detection and dosimetry of gamma ray emitted from Thallium-201 ( 201 Tl) and Technetium-99m ( 99m Tc) based on chemiluminescence technique. H 2 O 2 produced by two gamma emitter radioisotopes of 201 Tl and 99m Tc were quantitatively measured by chemiluminescence method. Upon producing H 2 O 2 in a luminol alkaline solution, in the presence of diperiodatocuprate, as catalyst a chemical reaction was accrued and consequently the emitted light was measured. The determined H 2 O 2 concentration was correlated with the gamma ray detection and dosimetry. The sensitivity of chemiluminescence technique for 201 Tl and 99m Tc dosimetry was determined to be 0.20 and 0.08 MBq/l (Mega Becquerel per liter) respectively (R.S.D. = %5, N = 3). The plotted calibration curves showed detection limits of 3.24 and 1.76 MBq/l for 201 Tl and 99m Tc, respectively.

A biosensor for detection of hydrogen peroxide was designed based on immobilization of anthraquinone 2-carboxylic acid modified horseradish peroxidase. Direct electrochemistry of the modified enzyme exhibited a quasi-reversible voltammogram with a formal potential of −459 mV. The surface charge transfer rate constant, k s , and the charge transfer coefficient, α c , for electron transfer between the glassy carbon electrode and the modified enzyme were estimated to be 3.165 s −1 and 0.455, respectively. The modified electrode exhibited a remarkable electrocatalytic activity towards hydrogen peroxide. Under the optimized experimental conditions, H 2 O 2 could be detected in a linear concentration range from 2.65 × 10 −9 to 1.08 × 10 −7 M and a detection limit of 1.44 × 10 −9 M at S/N = 3. The response time was 6 s and when the electrode was stored at 4 °C, the biosensor was used repeatedly for 17 days with 10% deterioration in response.

The formation of amyloid fibrils are thought to contribute to pathogenesis of many amyloids associated human diseases. Here the impact of curcumin on amyloid formation of human serum albumin (HSA) was studied. Incubation of HSA at 68°C under physiologic pH led to amyloid fibril formation. Thioflavin T (ThT) fluorescence was used for deter- mination of amyloid fibril formation. Atomic force microscopy experiments indicated different fibril structure of HSA in- cubated with or without curcumin. The monitoring of the changes in reactive oxygen species (ROS) levels upon incuba- tion of curcumin with HSA showed a significant decrease in ROS levels. Similar experiments were also carried out in the presence of aflatoxin M1 (AFM1) and lead (Pb) ions. Our results indicated that AFM1 and Pb ions promote the fibrillation of HSA and accelerate ROS production, which were inhibited in the presence of curcumin. Thus, curcumin mitigates pro- tein fibrillation activity and diminishes ROS generation.

Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV–Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.