Permeation behavior of porphyrin derivatives with different functional group positions across cancer cell membranes.

Porphyrin, which shows selective accumulation in cancer cells, has attracted attention as a drug carrier. The influences of the functional porphyrin positions (ß- and meso-positions) on porphyrin accumulation must be understood. In this work, we focused on the investigation of the phenyl functional group whose ß-position influences cancer cell accumulation through direct membrane permeation and endocytosis. The endocytic pathway, in particular, is influenced by both clathrin-dependent and caveolae-dependent endocytosis.

Cancer cell growth suppressibility of ω-3 fatty acid whose carboxy group converted to ester group.

Recently, ω-3 fatty acids have been revealed to having cancer cell growth suppressibility. It is necessary to analyze the mechanism of cancer cell growth suppressibility and to impart selective cancer cell accumulation when creating anticancer drugs based on ω-3 fatty acids. Therefore, it is necessarily essential to introduce a luminescent molecule or a molecule which have a drug delivery function into ω-3 fatty acids, and the position of introduction is the ω-3 fatty acids' carboxyl group. On the other hand, whether the ω-3 fatty acids' cancer cell growth suppressibility is maintained when the ω-3 fatty acids' carboxyl groups are converted to other structures, such as ester groups, is unclear. In this work, a derivative was synthesized wherein the α-linolenic acid carboxyl group, one of the ω-3 fatty acids, was converted to an ester group and evaluated the cancer cell growth suppressibility, as well as the amount of cancer cell uptake. As a result, it was suggested that the ester group derivatives presented the same functionality as α-linolenic acid, and the ω-3 fatty acid carboxyl group is a flexible functional group, which can be structurally modified in terms of functionality to cancer cells.

Correlations between functional porphyrin positions and accumulation in cancer cells.

Porphyrin is accumulated in tumours due to its interaction with protein. Cancer therapy with porphyrin as a carrier molecule is attracting attention. Porphyrin displays two functional sites termed ß- and meso-positions. A correlation between the functional position on the porphyrin molecule and the ability to accumulate in cancer cells is observed in the present study. The accumulation of porphyrin derivatives was determined by measuring fluorescence intensity after incubation for 2 and 24 h. The accumulation of cancer cells depended on the position and length of functional groups. Estimated binding constants between porphyrin and bovine serum albumin suggest that the position of functional groups leads to changes in binding affinity and influences the accumulation of porphyrin derivatives in cancer cells.

Synthesis of Mesoporous TiO2/Boron-Doped Diamond Photocatalyst and Its Photocatalytic Activity under Deep UV Light (λ = 222 nm) Irradiation.

There is a need for highly efficient photocatalysts, particularly for water purification. In this study, we fabricated a mesoporous TiO2 thin film on a boron-doped diamond (BDD) layer by a surfactant-assisted sol-gel method, in which self-assembled amphiphilic surfactant micelles were used as an organic template. Scanning electron microscopy revealed uniform mesopores, approximately 20 nm in diameter, that were hexagonally packed in the TiO2 thin film. Wide-angle X-ray diffraction and Raman spectroscopy clarified that the framework crystallized in the anatase phase. Current⁻voltage (I⁻V) measurements showed rectification features at the TiO2/BDD heterojunction, confirming that a p⁻n hetero-interface formed. The as-synthesized mesoporous TiO2/BDD worked well as a photocatalyst, even with a small volume of TiO2 (15 mm × 15 mm × c.a. 1.5 µm in thickness). The use of deep UV light (λ = 222 nm) as a light source was necessary to enhance photocatalytic activity, due to photo-excitation occurring in both BDD and TiO2.

DNase γ, DNase I and caspase-activated DNase cooperate to degrade dead cells.

Serum endonucleases are essential for degrading the chromatin released from dead cells and preventing autoimmune diseases such as systemic lupus erythematosus. Serum DNase I is known as the major endonuclease, but recently, another endonuclease, DNase γ/DNase I-like 3, gained attention. However, the precise role of each endonuclease, especially that of DNase γ, remains unclear. In this study, we distinguished the activities of DNase γ from those of DNase I in mouse serum and concluded that both cooperated in degrading DNA during necrosis: DNase γ functions as the primary chromatolytic activity, causing internucleosomal DNA fragmentation, and DNase I as the secondary one, causing random DNA digestion for its complete degradation. These results were confirmed by two in vivo experimental mouse models, in which necrosis was induced, acetaminophen-induced hepatic injury and streptozotocin-induced ß-cell necrosis models. We also determined that DNase γ functions as a backup endonuclease for caspase-activated DNase (CAD) in the secondary necrosis phase after γ-ray-induced apoptosis in vivo.

Enhanced Sensitivity for Electrochemical Detection Using Screen-Printed Diamond Electrodes via the Random Microelectrode Array Effect.

The electrochemical properties of screen-printed diamond electrodes with various insulating polyester (PES) resin binder/boron-doped diamond powder (BDDP) ratios were investigated for high sensitivity electrochemical detection. For PES/BDDP weight ratios in the range of 0.3-0.5, the BDDP-printed electrodes exhibited cyclic voltammetry (CV) characteristics for Fe(CN)6(3-/4-) that are typical of a planar electrode, whereas microelectrode-like characteristics with sigmoidal CV curves were observed for PES/BDDP ratios of 1.0-2.0. Cu elemental mapping images of copper-electrodeposited BDDP-printed electrodes indicated the formation of island structures with conductive BDDP domains surrounded by an insulating PES matrix for large PES/BDDP ratios. The electrochemical detection of ascorbic acid (AA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also investigated using polycrystalline BDD thin-film and BDDP-printed electrodes (PES/BDDP ratio = 0.3 and 1.0). As a result, the signal-to-background (S/B) ratios for the voltammetric detection of AA and 8-OHdG were in the order BDDP-printed electrode (PES/BDDP = 1.0) > BDDP-printed electrode (PES/BDDP = 0.3) > polycrystalline BDD thin film electrode, based on the large faradaic current with respect to the background current. Therefore, the BDDP-printed electrode with a large insulating binder/BDDP ratio has the potential for use as a disposable electrode for electrochemical detection. The electrode is cheaper, lighter and more sensitive than conventional BDD electrodes.

Intermolecular Interaction between Phosphatidylcholine and Sulfobetaine Lipid: A Combination of Lipids with Antiparallel Arranged Headgroup Charge.

Intermolecular interactions between lipid molecules are important when designing lipid bilayer interfaces, which have many biomedical applications such as in drug delivery vehicles and biosensors. Phosphatidylcholine, a naturally occurring lipid, is the most common lipid found in organisms. Its chemical structure has a negatively charged phosphate linkage, adjacent to an ester linkage in a glycerol moiety, and a positively charged choline group, placed at the terminus of the molecule. Recently, several types of synthetic lipids that have headgroups with the opposite charge to that of phosphatidylcholine have emerged; that is, a positively charged ammonium group is present adjacent to the ester linkage in their glycerol moiety and a negatively charged group is placed at their terminus. These types of lipids constitute a new class of soft material. The aim of this study was to determine how such lipids, with antiparallel arranged headgroup charge, interact with naturally occurring phosphatidylcholines. We synthesized 1,2-dipalmitoyl-sn-glycero-3-sulfobetaine (DPSB) to represent a reversed-head lipid; 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) was used to represent a naturally occurring phospholipid. The intermolecular interaction between these lipids was investigated using surface pressure-area (π-A) isotherms of the lipid monolayer at the air/water interface. We found that the extrapolated area and excess free energy of the mixed monolayer deviated negatively when compared with the ideal values from additivity. Moreover, differential scanning calorimetry of the lipid mixture in aqueous dispersion showed that the gel-to-liquid crystal transition temperature increased compared with that of each pure lipid composition. These results clearly indicate that DPSB preferably interacts with DPPC in the mixture. We believe that the attraction between the oppositely charged headgroups of these lipids reinforces the intermolecular interaction. Our results provide insight into the intermolecular interaction between phospholipids and reversed-head lipids, which may prove useful for the design of lipid-based materials in the future.

Direct determination of chemical oxygen demand by anodic decomposition of organic compounds at a diamond electrode.

Chemical oxygen demand (COD) was measured directly with a simple electrochemical method using a boron-doped diamond (BDD) electrode. By applying a highly positive potential (+2.5 V vs Ag/AgCl) to an aqueous electrolyte containing potassium hydrogen phthalate, glucose, and lactic acid or sodium dodecylbenzenesulfonate using a BDD electrode, an anodic current corresponding to the electrolytic decomposition of these organic compounds was observed. No such current was seen on glassy carbon or platinum electrodes due to a significant background current caused by the oxygen evolution reaction. The electric charge for the anodic current observed at the BDD electrode was found to be consistent with the theoretical charge required for the electrolytic decomposition of the organic compounds to CO2 and was used to calculate COD. This analysis was performed by a simple I-t measurement at constant potential using a BDD electrode, and no calibration was needed. This new simple indicator, "ECOD" (electrochemical oxygen demand), will be useful for continuous monitoring of industrial wastewater with low protein concentrations and on-site instant analysis of natural water with a BDD electrode-based portable ECOD meter.

Simultaneous glucose sensing and biohydrogen evolution from direct photoelectrocatalytic glucose oxidation on robust Cu2O-TiO2 electrodes.

We report simultaneous photoelectrocatalytic (PEC) glucose sensing and biohydrogen generation for the first time from the direct PEC oxidation of glucose at multifunctional and robust Cu2O-TiO2 photocatalysts. Striking improvement of 30% in overall H2 gas evolution (∼122 µmol h(-1) cm(-2)) by photoholes assisted glucose oxidation opens a new platform in solar-driven PEC biohydrogen generation.

Conceptual study on extraction of formic acid from the electrolyte after electroreduction of CO2: Desalination and dehydration using a high-silica chabazite zeolite membrane.

Here, we propose a two-step pervaporation system with a high-silica CHA (chabazite) membrane, which has sufficient resistance to water and acid, to demonstrate the extraction and condensation of the formic acid formed by electroreduction of CO2. The kinetic diameters of water and formic acid are similar and smaller than the pore size of CHA, while the hydrated electrolyte ions (e.g., K+ and Cl-) are larger than the pore size of CHA. Consequently, the electrolyte ions are separated from the mixture of water and formic acid in the first desalination process, and then water molecules are easily removed from the mixture in the second dehydration process. From 300 ml of an approximately 3 wt% formic acid aqueous solution containing 0.5 M KCl, 10 ml of 18.2 wt% formic acid was obtained.

Enhanced degradation of ibuprofen using a combined treatment of plasma and Fenton reactions.

Advanced oxidation technologies (AOTs) proved to be effective in the degradation of hazardous organic impurities like acids, dyes, antibiotics etc. in the last few decades. AOTs are mainly based on the generation of reactive chemical species (RCS) such as hydroxyl, superoxide radicals etc., which plays an important role in the degradation of organiccompounds. In this work, plasma supported AOT i.e. Fenton reactions have been applied for the degradation of ibuprofen. As compared to traditional AOTs plasma assisted AOT is technologically superior due to its capability to produce RCS at a controlled rate without using chemical agents. This process work at normal room temperature and pressure. Herein, we optimized better operating conditions to generate good plasma discharge and hydroxyl radicals based on critical parameters, including frequency, pulse width and different gases like O2, Ar etc. Also, the one-pot carbonization method is used for the synthesis of Fe-based ordered mesoporous carbon (OMC) as a heterogeneous catalyst for the Fenton reactions. Using plasma-supported Fenton reactions, 88.3 % degradation efficiency is achieved using Fe-OMC catalyst for the ibuprofen degradation. Also, the mineralization of the ibuprofen is studied using total organic carbon (TOC) analysis.

Evaluation of the Correlation between Porphyrin Accumulation in Cancer Cells and Functional Porphyrin Positions of the Phenyl Group.

Porphyrin selectively shows tumour accumulation and has attracted attention as a carrier molecule for drug delivery systems (DDS). Porphyrin has two functional sites termed the meso- and ß-positions. In previous work, meso-porphyrin derivatives with an alkyl group were found to exhibit greater accumulation in human breast cancer cells (MCF-7). To identify the correlation between porphyrin accumulation and functional porphyrin positions of other functional groups, the accumulation of porphyrin derivatives with a phenyl group was investigated. The ß-porphyrin derivative with a phenyl group showed higher accumulation in MCF-7 cells and greater affinity for albumin than the meso-porphyrin derivative. The results of density functional theory (DFT) calculations suggest that the ß-porphyrin derivative with a phenyl group had higher planarity across the total structure than the meso-porphyrin derivative. It was concluded that the greater planarity of the ß-porphyrin derivative with a phenyl group might lead to superior MCF-7 cell accumulation.

Evaluation of Cancer Cell Growth Suppressibility of ω-3 Fatty Acids and Their Metabolites.

According to current research, cancer cell growth is suppressed by ω-3 fatty acids, which are essential fatty acids. On the other hand, ω-3 fatty acids are metabolized to bioactivities in vivo. A systematic evaluation of the ability of ω-3 fatty acids and their metabolites to suppress cancer cell growth has not been sufficiently conducted. Our work evaluated the effect of ω-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid), trans fatty acid, and the metabolites (Resolvin E1, Maresin 1) on cancer cell growth suppressibility. Our results suggest that there may be optimal fatty acids depending on the kind of cancer cells, the presence or absence of hydroxyl group, and the double bond structure involved.

Interactions between pH, reactive species, and cells in plasma-activated water can remove algae.

Lightning strikes cause nitrogen to dissolve in water and form reactive nitrogen and oxygen species, which form natural fertilizers that can be absorbed through plant roots. Such processes during rainstorm events can be simulated by applying plasma to a solution. Plasma-activated water (PAW) has great potential as a source of various dissolved reactive chemical species. Different mixtures of species are produced using different solution compositions. Here, basil seeds were grown in PAW to prevent blooms of Chlorella vulgaris and ion chromatography and UV-vis spectroscopy were used to quantify reactive ions. NO2 -, NO3 -, and H2O2 were found to be key to the antialgal effect. Secondary reactive ions such as peroxynitrite (ONOO-, ONOOH) were also involved. The antialgal effect was strongly related to the pH around the algal cells. Acidification was predominantly caused by the generation of NO2 - and H2O2. After two weeks monitoring basil growth, the antifungal properties were preserved, few reactive oxygen species formed in the plasma zone, and only reactive nitrogen species were transformed into reactive peroxynitrite ions. The pH around the cells was determined using an iridium oxide microelectrode. The PAW antialgal mechanism depended on acidic conditions (pH 2.2, at which peroxynitrite can be generated) under which ONOOH penetrated the algal cell membranes, destroying the cells and preventing growth. This practical and sustainable PAW process allows a surprising amount of fertilizer to be generated with an antialgal effect that could be used in various eco-friendly agricultural processes under ambient conditions.

Complete decomposition of sulfamethoxazole during an advanced oxidation process in a simple water treatment system.

A simple water treatment system consisting of a deep UV light (λ = 222 nm) source, a mesoporous TiO2/boron-doped diamond (BDD) photocatalyst, and a BDD electrode was prepared and used to decompose sulfamethoxazole (SMX) in an advanced oxidation process. The mesoporous TiO2/BDD photocatalyst used with the electrochemical treatment promoted SMX decomposition, but the mesoporous TiO2/BDD photocatalyst alone had a similar ability to decompose SMX as photolysis. Fragments produced through photocatalytic treatment were decomposed during the electrochemical treatment and fragments produced during the electrochemical treatment were decomposed during the photocatalytic treatment, so performing the electrochemical and photocatalytic treatments together effectively decomposed SMX and decrease the total organic carbon concentration to a trace.

Evaluation of the correlation between porphyrin accumulation in cancer cells and functional positions for application as a drug carrier.

Porphyrin derivatives accumulate selectively in cancer cells and are can be used as carriers of drugs. Until now, the substituents that bind to porphyrins (mainly at the meso-position) have been actively investigated, but the effect of the functional porphyrin positions (ß-, meso-position) on tumor accumulation has not been investigated. Therefore, we investigated the correlation between the functional position of substituents and the accumulation of porphyrins in cancer cells using cancer cells. We found that the meso-derivative showed higher accumulation in cancer cells than the ß-derivative, and porphyrins with less bulky substituent actively accumulate in cancer cells. When evaluating the intracellular distribution of porphyrin, we found that porphyrin was internalized by endocytosis and direct membrane permeation. As factors involved in these two permeation mechanisms, we evaluated the affinity between porphyrin-protein (endocytosis) and the permeability to the phospholipid bilayer membrane (direct membrane permeation). We found that the binding position of porphyrin affects the factors involved in the transmembrane permeation mechanisms and impacts the accumulation in cancer cells.

Urinary trypsin inhibitor suppresses excessive generation of superoxide anion radical, systemic inflammation, oxidative stress, and endothelial injury in endotoxemic rats.

OBJECTIVE AND DESIGN: The protective effects of ulinastatin, a human urinary trypsin inhibitor (UTI), against superoxide radical (O(2)(-*)) generation, systemic inflammation, lipid peroxidation, and endothelial injury were investigated in endotoxemic rats. MATERIALS AND TREATMENT: Twenty-one Wistar rats were allocated to a control group, a UTI group, and a sham group. A bolus of lipopolysaccharide (LPS; 3 microg/g) was administered intravenously to the control group, a bolus of LPS and UTI (5 U/g) to the UTI group, and a bolus of saline to the sham group. METHODS: The O(2)(-*) generated was measured as the current in the right atrium using an electrochemical O(2)(-*) sensor. Plasma nitrite, high mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, malondialdehyde, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured 360 min after LPS administration. RESULTS: The O(2)(-*) current increased in the control group and was significantly attenuated in the UTI group after 55 min (P < 0.05 at 55-60 min, P < 0.01 at 65-360 min). Plasma nitrite, HMGB1, TNF-alpha, IL-6, malondialdehyde, and sICAM-1 were attenuated in the UTI group. CONCLUSIONS: UTI suppressed excessive O(2)(-*) generation, systemic inflammation, lipid peroxidation, and endothelial injury in endotoxemic rats.

Synergetic effect in water treatment with mesoporous TiO2/BDD hybrid electrode.

Boron-doped diamond (BDD) electrodes have a wide potential window and can produce ozone by water electrolysis at high voltage. Though ozone has strong oxidative power (standard oxidation potential: 2.07 V vs. NHE), it cannot decompose certain types of recalcitrant organic matter completely. We developed an advanced oxidation process (AOP), in which hydroxy radicals with stronger oxidative power (standard oxidation potential: 2.85 V vs. NHE) are formed using a combination of ozone, photocatalyst, and UV. In this study, we fabricated a mesoporous TiO2/BDD hybrid electrode and examined its potential for AOPs. A synergetic effect between electrochemical water treatment and photocatalytic water treatment was observed with the hybrid electrode that did not occur with the BDD electrode.

Boron-doped Nanodiamond as an Electrode Material for Aqueous Electric Double-layer Capacitors.

Herein, a conductive boron-doped nanodiamond (BDND) particle is prepared as an electrode material for an aqueous electric double-layer capacitor with high power and energy densities. The BDND is obtained by depositing a boron-doped diamond (BDD) on a nanodiamond particle substrate with a primary particle size of 4.7 nm via microwave plasma-assisted chemical vapor deposition, followed by heat treatment in air. The BDND comprises BDD and sp2 carbon components, and exhibits a conductivity above 10-2 S cm-1 and a specific surface area of 650 m2 g-1. Cyclic voltammetry measurements recorded in 1 M H2SO4 at a BDND electrode in a two-electrode system shows a capacitance of 15.1 F g-1 and a wide potential window (cell voltage) of 1.8 V, which is much larger than that obtained at an activated carbon electrode, i.e., 0.8 V. Furthermore, the cell voltage of the BDND electrode reaches 2.8 V when using saturated NaClO4 as electrolyte. The energy and power densities per unit weight of the BDND for charging-discharging in 1 M H2SO4 at the BDND electrode cell are 10 Wh kg-1 and 104 W kg-1, respectively, and the energy and power densities per unit volume of the BDND layer are 3-4 mWh cm-3 and 10 W cm-3, respectively. Therefore, the BDND is a promising candidate for the development of a compact aqueous EDLC device with high energy and power densities.

Preparation of pH-sensitive liposomes retaining SOD mimic and their anticancer effect.

We prepared an anticancer drug based on a pH-sensitive liposome retaining Fe-porphyrin as an SOD mimic. The liposomes contained cationic/anionic lipid combinations and were composed of Fe-porphyrin, 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine, dimethylditetradecylammonium bromide, sodium oleate, and Tween-80. The Fe-porphyrin was released from the liposome at low pH, and the cytotoxicity for cancer cells by the liposome depended on the acidic environments of the endosomes in the cells. Furthermore, although the liposome exhibited an excellent anticancer effect on a gastric cancer cell line, the SOD activity of Fe-porphyrin was shown to have a significant influence on the cytotoxicity toward cancer cells. These findings suggest that the pH-sensitive liposome retaining the Fe-porphyrin as an SOD mimic promises to be a novel anticancer drug for endosomal escape.