Adsorptive removal of oxytetracycline using MnO2-engineered pine-cone biochar: thermodynamic and kinetic investigation and process optimization.

Indiscriminate use of oxytetracycline is linked to the development of antibiotic-resistant genes, posing a serious threat to human health and ecosystem balance. This article reports the adsorptive elimination of oxytetracycline (OTC) from aqueous solution using a newly developed MnO2-modified pine-cone biochar (MnO2/PCBC). The MnO2/PCBC was characterized using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, CHNS analyzer, inductively coupled plasma-optical emission spectroscopy, and Brunauer-Emmett-Teller N2 adsorption analyzer. Batch adsorption experiments, designed using the central composite design framework of response surface methodology, were conducted to investigate the influence of process variables on the adsorption of OTC onto MnO2/PCBC. The optimized conditions for achieving maximum removal (88.1%) were found to be at pH 8, MnO2/PCBC dose 0.44 g/L, initial OTC concentration 200 mg/L, and temperature 303 K. The adsorption process follows Langmuir (R2=0.95) and Freundlich (R2=0.95) isotherms and pseudo-second-order (R2=0.99) adsorption kinetics. The adsorption process was found to be endothermic (ΔH0 = 33.04 kJ/mol) and spontaneous in nature (ΔG0 from -1.33 kJ/mol at 283 K to -5.65 kJ/mol at 313 K). The synthesized MnO2/PCBC could be recycled and reused for OTC removal with a percentage removal of around 80% after fifth cycle. The results indicate an effective removal of oxytetracycline with only 0.44 g/L MnO2/PCBC with maximum adsorption capacity of 357.14 mg/g which demonstrates improved performance in comparison to many adsorbents reported in literature. This implies that MnO2/PCBC offers potential to be developed into a cost-effective technique for antibiotic removal from water.

Targeted Delivery of siRNA Therapeutics using Ligand Mediated Biodegradable Polymeric Nanocarriers.

BACKGROUND: Cancer poses a major public health issue, is linked with high mortality rates across the world, and shows a strong interplay between genetic and environmental factors. To date, common therapeutics, including chemotherapy, immunotherapy, and radiotherapy, have made significant contributions to cancer treatment, although diverse obstacles for achieving the permanent "magic bullet" cure have remained. Recently, various anticancer therapeutic agents designed to overcome the limitations of these conventional cancer treatments have received considerable attention. One of these promising and novel agents is the siRNA delivery system; however, poor cellular uptake and altered siRNA stability in physiological environments have limited its use in clinical trials. Therefore, developing the ideal siRNA delivery system with low cytotoxicity, improved siRNA stability in the body's circulation, and prevention of its rapid clearance from bodily fluids, is rapidly emerging as an innovative therapeutic strategy to combat cancer. Moreover, active targeting using ligand moieties which bind to over-expressed receptors on the surface of cancer cells would enhance the therapeutic efficiency of siRNA. CONCLUSION: In this review, we provide 1) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and 2) a description of the five major cancer-targeting ligands.

Quantitative classification of DNA damages induced by submicromolar cadmium using oligonucleotide chip coupled with lesion-specific endonuclease digestion.

Implementation of proper analytical tool for systematic investigation and quantitative determination of different classes of cadmium ion-induced DNA damages, especially at low metal ion concentrations, is still lacking. Using lesion-specific enzymes that cleave DNA at specific classes of damage and a fluorometric approach developed for quantifying fluorophore-labeled oligonucleotides bound to chip surfaces, we determined the frequencies of different lesions (strand breaks, oxidized purines, oxidized pyrimidines, or abasic sites) induced by submicromolar Cd(2+). Cd(2+)-treated oligonucleotide chips were digested with various endonucleases (Fpg protein, endonuclease III, endonuclease IV), producing a de novo single strand break (SSB) at their substrate modifications. The frequency of SSB and double strand break (DSB) was computed from the difference of pre- and post-Cd(2+)-treatment oligonucleotide coverage on the chip. While the frequency of SSBs and oxidized bases were successfully quantified even at 0.5 µM of Cd(2+), DSB frequency could be easily quantitated at 8.7 µM [Cd(2+)]. The numbers of abasic sites were below the oligonucleotide detection limit (2.4 amole; equivalent to 0.24 fM for a reaction volume of 100 µL). SSBs were found to constitute about 85-90% of single strand damages, while oxidized bases comprise only 4-7% of the total at 0.9 to 8.7 µM [Cd(2+)].

High-content screening of drug-induced cardiotoxicity using quantitative single cell imaging cytometry on microfluidic device.

Drug-induced cardiotoxicity or cytotoxicity followed by cell death in cardiac muscle is one of the major concerns in drug development. Herein, we report a high-content quantitative multicolor single cell imaging tool for automatic screening of drug-induced cardiotoxicity in an intact cell. A tunable multicolor imaging system coupled with a miniaturized sample platform was destined to elucidate drug-induced cardiotoxicity via simultaneous quantitative monitoring of intracellular sodium ion concentration, potassium ion channel permeability and apoptosis/necrosis in H9c2(2-1) cell line. Cells were treated with cisapride (a human ether-à-go-go-related gene (hERG) channel blocker), digoxin (Na(+)/K(+)-pump blocker), camptothecin (anticancer agent) and a newly synthesized anti-cancer drug candidate (SH-03). Decrease in potassium channel permeability in cisapride-treated cells indicated that it can also inhibit the trafficking of the hERG channel. Digoxin treatment resulted in an increase of intracellular [Na(+)]. However, it did not affect potassium channel permeability. Camptothecin and SH-03 did not show any cytotoxic effect at normal use (≤300 nM and 10 µM, respectively). This result clearly indicates the potential of SH-03 as a new anticancer drug candidate. The developed method was also used to correlate the cell death pathway with alterations in intracellular [Na(+)]. The developed protocol can directly depict and quantitate targeted cellular responses, subsequently enabling an automated, easy to operate tool that is applicable to drug-induced cytotoxicity monitoring with special reference to next generation drug discovery screening. This multicolor imaging based system has great potential as a complementary system to the conventional patch clamp technique and flow cytometric measurement for the screening of drug cardiotoxicity.

Development of radiation indicators to distinguish between irradiated and non-irradiated herbal medicines using HPLC and GC-MS.

The effects of high dose γ-irradiation on six herbal medicines were investigated using gas chromatography-mass spectrometry (GC/MS) and high-performance liquid chromatography (HPLC). Herbal medicines were irradiated at 0-50 kGy with (60)Co irradiator. HPLC was used to quantify changes of major components including glycyrrhizin, cinnamic acid, poncirin, hesperidin, berberine, and amygdalin in licorice, cinnamon bark, poncirin immature fruit, citrus unshiu peel, coptis rhizome, and apricot kernel. No significant differences were found between gamma-irradiated and non-irradiated samples with regard to the amounts of glycyrrhizin, berberine, and amygdalin. However, the contents of cinnamic acid, poncirin, and hesperidin were increased after irradiation. Volatile compounds were analyzed by GC/MS. The relative proportion of ketone in licorice was diminished after irradiation. The relative amount of hydrocarbons in irradiated cinnamon bark and apricot kernel was higher than that in non-irradiated samples. Therefore, ketone in licorice and hydrocarbons in cinnamon bark and apricot kernel can be considered radiolytic markers. Three unsaturated hydrocarbons, i.e., 1,7,10-hexadecatriene, 6,9-heptadecadiene, and 8-heptadecene, were detected only in apricot kernels irradiated at 25 and 50 kGy. These three hydrocarbons could be used as radiolytic markers to distinguish between irradiated (>25 kGy) and non-irradiated apricot kernels.

Determination of the dose-depth distribution of proton beam using resazurin assay in vitro and diode laser-induced fluorescence detection.

In this study the dose-depth distribution pattern of proton beams was investigated by inactivation of human cells exposed to high-LET (linear energy transfer) protons. The proton beams accelerated up to 45 MeV were horizontally extracted from the cyclotron, and were delivered to the cells acutely through a home made prototype over a range of physical depths (in the form of a variable water column). The biological systems used here were two in vitro cell lines, including human embryonic kidney cells (HEK 293), and human breast adenocarcinoma cell line (MCF-7). Cells were exposed to unmodulated proton beam radiation at a dose of 50 Gy similar to that used in therapy. Resazurin metabolism assay was investigated for measurement of cell response to irradiation as a simple and non-destructive assay. In the resazurin reduction test the non-fluorescent probe dye is reduced to pink and highly fluorescent resorufin. The dose-depth distribution of proton beam obtained based on the highly sensitive laser-induced fluorometric determination of resorufin was found to coincide well with the data collected using conventional film based dosimetry. The resazurin method yielded data comparable with the optical micrographs of the irradiated cells, showing the least cell survival at the measured Bragg-peak position of 10 mm. In addition, fused silica capillary was used as a sample container to increase the probability for irradiated laser beam to probe and excite resorufin in small sample volume of the capillary. The developed method has the potential to serve as a non-destructive, sample-thrifty, and time saving tool to realize more realistic, practical dose-depth distribution of proton beam compared to conventional in vitro cell viability assessment techniques.