Modification of Wiener Index and its application

A novel topological index based on the Wiener Index is proposed as W* = 1/2 sigma (n)(i,j=1) S(*)(ij), the element S(*)(ij) of the distance matrix is defined either as S(*)(ij) = alpha x square root of I(i)I(j)/R(ij) (atoms i and j are adjacent) or as S(*)(ij) = = alpha x (j-i+1)square root of I(i) x x x x x I(j)/R(ij) (atoms i and j are not adjacent), where I(i) and I(j) represent the electronegativity of vertices i or j, respectively, R(ij)() is the sum of the bond length between the vertices i and j in a molecular graph, and alpha = (Z(i)/Z(j))(0.5), where Z(i) and Z(j) are the atomic numbers of the positive valence atom i and the negative valence atom j, respectively. The properties and the interaction of the vertices in a molecule are taken into account in this definition. That is why the application of the index W to heteroatom-containing and multiple bond organic systems and inorganic systems is possible. Correlation coefficients above 0.97 are achieved in the prediction of the retention index of gas chromatography of the hydrocarbons, the standard formation enthalpy of methyl halides, halogen-silicon, and inorganic compounds containing transition metals.     

Quantitative Detection of PremicroRNA-21 Based on Chimeric Molecular Beacon

As an important tumor marker, the expression level of premicroRNA-21 (pre-miR-21) can provide important information for early diagnosis, drug treatment and prognosis of tumor. Thus, developing pre-miR-21 detection is of great importance for diagnosis of disease. Herein, a direct, simple and rapid method for quantitative detection of pre-miR-21 was developed. This detecting system contained the tool of molecular beacon which could hybridize specifically with pre-miR-21 and form duplex to induce fluorescence signal change. When loop bases hybridized with the pre-miR-21 in the solution to form a double-stranded duplex, the fluorophore and the quencher was separated and caused fluorescence recovery. We developed the new method for pre-miR-21 assay with detection limit of 0.5 nM. Under the optimal conditions, the method was used to detect the level of pre-miR-21 in different tumor cells and tissues. The results showed that pre-miR-21 level was tightly related with tumor cells origins and malignancy degree. In 16 cases of gastric cancer tissues and adjacent tissues, the level of pre-miR-21 in 12 cases of cancer tissues was higher than that of adjacent tissues; 3 cases had lower expression level than that of adjacent tissues, and 1 case had no significant difference. Furthermore, Quantitative real-time PCR (qRT-PCR) method was used in to confirm the reliability of the detection results. The consistent results of the two different methods clearly showed that the molecular beacon assay with advantages of simplicity and rapidity for pre-miR-21 detection was hopeful for the wide usability in the function research and clinical diagnosis of pre-microRNA.     

Detection of Early Stages of Carcinogenesis in Adenomas of Murine Lung by 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence

Abstract— Administration of the heme precursor 5-aminolevulinic acid (ALA) leads to the selective accumulation of the photosensitizer protoporphyrin IX (PpIX) in certain types of normal and abnormal tissues. This phenomenon has been exploited clinically for detection and treatment of a variety of malignant and nonmalignant lesions. The present preclinical study examined the specificity of ALA-induced porphyrin fluorescence in chemically induced murine lung tumors in vivo. During the early stages of tumorigenesis, ALA-induced PpIX fluorescence developed in hyperplastic tissues in the lung and later in early lung tumor foci. In early tumor foci, maximum PpIX fluorescence occurred 2 h after the administration of ALA and returned to background levels after 4 h. There was approximately a 20-fold difference in PpIX fluorescence intensity between tumor foci and the adjacent normal tissue. The specificity of ALA-induced fluorescence for hyperplastic tissues and benign tumors in lung during tumorigenesis suggests a possible use for this fluorochrome in the detection of premalignant alterations in the lung by fluorescence endoscopy. Two non-small cell lung cancer cell lines developed ALA-induced PpIX fluorescence in vitro . These lines exhibited a light-dose-dependent phototoxic response to ALA photodynamic therapy (PDT) in vitro . Because PpIX is a clinically effective photosensitizer for a wide variety of malignancies, these results support the possible use of ALA-induced PpIX PDT for lung cancer.     

Systemic application of photosensitizers in the chick chorioallantoic membrane (CAM) model: photodynamic response of CAM vessels and 5-aminolevulinic acid uptake kinetics by transplantable tumors.

The aim of this study is to modify the chick chorioallantoic membrane (CAM) model into a whole-animal tumor model for photodynamic therapy (PDT). By using intraperitoneal (i.p.) photosensitizer injection of the chick embryo, use of the CAM for PDT has been extended to include systemic delivery as well as topical application of photosensitizers. The model has been tested for its capability to mimic an animal tumor model and to serve for PDT studies by measuring drug fluorescence and PDT-induced effects. Three second-generation photosensitizers have been tested for their ability to produce photodynamic response in the chick embryo/CAM system when delivered by i.p. injection: 5-aminolevulinic acid (ALA), benzoporphyrin derivative monoacid ring A (BPD-MA), and Lutetium-texaphyrin (Lu-Tex). Exposure of the CAM vasculature to the appropriate laser light results in light-dose-dependent vascular damage with all three compounds. Localization of ALA following i.p. injections in embryos, whose CAMs have been implanted with rat ovarian cancer cells to produce nodules, is determined in real time by fluorescence of the photoactive metabolite protoporphyrin IX (PpIX). Dose-dependent fluorescence in the normal CAM vasculature and the tumor implants confirms the uptake of ALA from the peritoneum, systemic circulation of the drug, and its conversion to PpIX.     

PHOTODYNAMIC ACTIVITIES and SKIN PHOTOSENSITIVITY OF THE bis(DIMETHYLTHEXYLSILOXY)SILICON 2,3-NAPHTHALOCYANINE IN MICE

The photodynamic therapy (PDT) activity of the bis(dimethylthexylsiloxy)silicon 2,3-na-phthalocyanine (SiNc 8 ) was evaluated against the EMT-6 tumor implanted intradermally in BALB/c mice. The SiNc 8 was formulated in aqueous emulsions based on Cremophor EL or Solutol HS 15. The formulation was shown to affect plasma clearance and overall pharmacokinetics. Compared to Cremophor, Solutol promoted rapid plasma clearance and high liver retention of the dye, combined with a slight increase of dye tumor concentrations. The PDT action spectrum for tumor response of SiNc 8 in Cremophor (190 mW cm², 200 J cm², 24 h postinjection [p.i.] of 1 (jimol kg¹) showed a maximum at 780 nm, which corresponds to the absorption maximum of the monomelic dye as well as the in vivo maximum change in the “diffuse optical density” produced by the dye. The extent of tumor necrosis increased with augmented dye and light doses. Regardless of the formulation, at 1 h p.i. of 0.1 μmol kg^?! SiNc 8 , PDT efficiency (190 mW cm'², 400 J cm²) was high but accompanied by severe damage to normal tissues, at 24 h PDT resulted in complete tumor regression in 80% of the animals without adverse effects to adjacent tissues, while at 72 h p.i. PDT induced no tumor response with Cremophor and only a partial response with Solutol. At the latter time point, plasma dye clearance was nearly complete while tumor tissue levels remained high, suggesting that tumor response correlates with plasma rather than tumor dye levels. Skin sensitivity of SKhl mice to solar-simulated radiation was lower with SiNc 8 as compared to Photofrin®. Our data suggest the potential of SiNc 8 as a far-red absorbing photosensitizer in clinical PDT.     

Isosorbide‐based polysebacates as polymeric components for development of in situ forming implants

In situ forming implants (ISFIs) appear to be a convenient drug delivery system, alternative to conventional preformed implants and microparticles for parenteral drug delivery applications. It has been shown that they offer several advantages including easy and minimally invasive application, potential for local/site‐specific drug delivery that allows reduction of side effects associated with systemic administration of drug. A few ISFI formulations based on poly(α‐hydroxy acids), solidifying by solid phase separation, are currently commercially available. In this work, polyesters based on sebacic acid, isosorbide, and optionally 1,2‐propanediol were synthesized and characterized. Poly(isosorbide sebacate‐co‐1,2‐propylene sebacate) (PISEBPG) was chosen as an essential constituent of new ISFI formulations dedicated to controlled release of doxycycline hyclate (DOXY). Basic characteristics of new ISFI formulations were investigated. In particular, the influence of addition of a relatively hydrophobic cosolvent (triacetin, TA) to a more hydrophilic 1‐methyl‐2‐pyrrolidone (NMP) as well as the presence of calcium carbonate (CAC) on the morphology of resulted depots and DOXY release profile was evaluated. Scanning electron microscopy (SEM) analysis revealed that the presence of TA resulted in more porous morphology of the depots. DOXY has been releasing continuously from depots in vitro within 12 weeks depending on the composition. The release profile of the PISEBPG‐based formulation containing CAC indicates that it could be useful where short‐term (up to 14 d), rapid release of the antibiotic is required, while formulation without CAC, where after 21 days about 50% of the drug loaded may still be available for release, may be better for the long‐term delivery of DOXY.     

Metabolomic investigation of gastric cancer tissue using gas chromatography/mass spectrometry

Gastric cancer screening or diagnosis is mainly based on endoscopy and biopsy. The aim of this study was to identify the difference of metabolomic profile between normal and malignant gastric tissue, and to further explore tumor biomarkers. Chemical derivatization together with gas chromatography/mass spectrometry (GC/MS) was utilized to obtain the metabolomic information of the malignant and non-malignant tissues of gastric mucosae in 18 gastric cancer patients. Acquired metabolomic data was analyzed using the Wilcoxon rank sum test to find the tissue metabolic biomarkers for gastric cancer. A diagnostic model for gastric cancer was constructed using principal component analysis (PCA), and was assessed with receiver-operating characteristic (ROC) curves. Results showed that 18 metabolites were detected differently between the malignant tissues and the adjacent non-malignant tissues of gastric mucosa. Five metabolites were also detected differently between the non-invasive tumors and the invasive tumors. The diagnostic model could discriminate tumors from normal mucosae with an area under the curve (AUC) value of 0.9629, and another diagnostic model constructed for clinical staging was assessed with an AUC value of 0.969. We conclude that the metabolomic profile of malignant gastric tissue was different from normal, and that the selected tissue metabolites could probably be applied for clinical diagnosis or staging for gastric cancer.     

Synthesis of 3-(1-Cyclohexenyl)-2-butanone via Environmentally Friendly Catalysts

Introduction3- ( 1 - Cyclohexenyl) - 2 - butanone( CHB) is oneofthe importantchemicals and has a potential valuein perfume industry.Beak et al.[1] reported thatthe acylation of ethylidenecyclohexane( EDC) withzinc chloride as a catalystgave3- ( 1 - cyclohexenyl) -2 - butanone in a good yield,butthey have notmadea more detailed investigation.The use of such aconventional catalyst as zinc chloride leads to anumber of problems such as corrosion,unclean re-action products and the disposal of pot…     

In vivo fluorescence imaging in the second near-infrared window with long circulating carbon nanotubes capable of ultrahigh tumor uptake

Cancer imaging requires selective high accumulation of contrast agents in the tumor region and correspondingly low uptake in healthy tissues. Here, by making use of a novel synthetic polymer to solubilize single-walled carbon nanotubes (SWNTs), we prepared a well-functionalized SWNT formulation with long blood circulation (half-life of ～30 h) in vivo to achieve ultrahigh accumulation of ～30% injected dose (ID)/g in 4T1 murine breast tumors in Balb/c mice. Functionalization dependent blood circulation and tumor uptake were investigated through comparisons with phospholipid-PEG solubilized SWNTs. For the first time, we performed video-rate imaging of tumors based on the intrinsic fluorescence of SWNTs in the second near-infrared (NIR-II, 1.1-1.4 μm) window. We carried out dynamic contrast imaging through principal component analysis (PCA) to immediately pinpoint the tumor within ～20 s after injection. Imaging over time revealed increasing tumor contrast up to 72 h after injection, allowing for its unambiguous identification. The 3D reconstruction of the SWNTs distribution based on their stable photoluminescence inside the tumor revealed a high degree of colocalization of SWNTs and blood vessels, suggesting enhanced permeability and retention (EPR) effect as the main cause of high passive tumor uptake of the nanotubes.     

Clonazepam quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry in a bioequivalence study

A rapid, sensitive and specific method for quantifying clonazepam in human plasma using diazepam as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using a hexane/diethylether (20 : 80, v/v) solution. The extracts were analysed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS-MS). Chromatography was performed on a Jones Genesis C8 4 microm analytical column (100 x 2.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 0.5-50 ng/ml (r2 > 0.9965). The limit of quantification was 0.5 ng/ml. This HPLC/MS/MS procedure was used to assess the bioequivalence of two clonazepam 2 mg tablet formulations (clonazepam test formulation from Ranbaxy Laboratories Ltd and Rivotril from Roche Laboratórios Ltda as standard reference formulation).     

Unique dual fluorescence of sterically congested hexaalkyl benzenehexacarboxylates: mechanism and application to viscosity probing

The static and dynamic fluorescence behavior of a series of hexaalkyl benzenehexacarboxylates (R(6)BHC; R = methyl (Me), tert-butyl (tBu), (-)-menthyl (Men), (-)-bornyl (Bor), (-)-1-methylheptyl (MHp), neopentyl (neoPn), and 2-adamantyl (Ad)) was studied by steady-state and time-resolved fluorescence spectroscopy. Dual fluorescence from both the partially relaxed metastable Franck-Condon-like (FC') and the fully relaxed (RX) state was observed for tBu(6)BHC, Men(6)BHC, Bor(6)BHC, MHp(6)BHC, neoPn(6)BHC, and Ad(6)BHC, whereas only single fluorescence from the RX state was observed for Me(6)BHC. Picosecond time-resolved fluorescence spectroscopic measurements clearly demonstrated that the initially formed Franck-Condon (FC) state sequentially converts to the FC' and then to RX state, with the relaxation hindered to such an extent that it shows variation with the steric bulk of the R groups. Thus, the fluorescence lifetimes (tau's) of FC' and RX are critically dependent on the bulkiness of the R groups, varying from 17 to 130 ps and from 0.6 to 1.1 ns, respectively. The relative intensity of FC' and RX fluorescence (I(RX)/I(FC)(')) was found to be dependent on the excitation wavelength, suggesting that the conformational relaxation from the FC' to RX state can compete with the vibrational relaxation of the FC' state. The temperature and pressure dependences were studied by steady-state fluorescence spectroscopy to give the activation energies of 1-3 kcal/mol for the FC'-to-RX relaxation of congested R(6)BHCs, as well as the activation volumes of 2.0, -0.62, and 7.4 mL/mol for tBu(6)BHC, Men(6)BHC, and Bor(6)BHC at room temperature. The fluorescence anisotropy (rho), as a measure of molecular motion, was also determined to be in the ranges of 0.03-0.3 for FC' and 0.003-0.01 for RX. The much larger rho's for the FC' fluorescence by a factor of 2-100 are attributed to the shorter tau's. The I(RX)/I(F' ratio was found to be insensitive to solvent polarity, but critically dependent on solvent viscosity, exhibiting an excellent linear relationship with the reciprocal viscosity. The potential use of these sterically congested R(6)BHCs as microenvironmental viscosity probes is proposed.     

The solubilisation behaviour of some dichloroalkanes in aqueous solutions of PEO-PPO-PEO triblock copolymers: a dynamic light scattering, fluorescence spectroscopy, and SANS study

The aggregation behaviour of PEO-PPO-PEO triblock copolymers in water and in water + chlorinated additive mixtures was studied by means of fluorescence spectroscopy, dynamic light scattering (DLS), and small-angle neutron scattering (SANS). The copolymers were chosen such as to investigate the effects of molecular architecture (L35 and 10R5) and molecular weight by keeping constant the hydrophilic/hydrophobic balance (F88 and F108). 1,2-Dichloroethane was used as a prototype of water basins contaminants. The hydrodynamic radius of the block copolymer aggregates (R(h,M)) and the intensity ratio of pyrene of the first and the third vibrational band (I(1)/I(3)) were determined as a function of temperature (10-45 degrees C) and concentration. The copolymer architecture essentially does not affect R(h,M) in the entire range of temperature and concentration investigated. At a given temperature, increasing macromolecular size leads to a decrease of R(h,M). With rising temperature R(h,M) also decreases. According to the DLS results, the I(1)/I(3) change with temperature clearly detects the aggregation only for F88 and F108. The presence of 1,2-dichloroethane, at concentrations close to its solubility in water, does not lead to changes in the distribution of hydrodynamic radii for L35 and 10R5. Larger quantities of additive induce the formation of quite polydisperse mixed aggregates for L35 and of networks for 10R5. In the case of F88 and F108, low concentrations of additive lead to formation of mixed aggregates with smaller R(h,M). The SANS results corroborate the DLS and fluorescence findings proving enhancement of the copolymer aggregation through the presence of 1,2-dichloroethane. The DLS findings combined with those from the fluorescence spectroscopy provide some insight into the site of solubilisation of the additive in the aggregates.     

Determination of AJ-3941, a possible agent for the treatment of cerebrovascular disorders, in plasma and brain by means of high-performance liquid chromatography with fluorescence detection.

A sensitive and selective high-performance liquid chromatographic method with fluorescence detection is described for the determination of AJ-3941 (I), a possible agent for the treatment of cerebrovascular disorders, in plasma and brain tissue. A simple hexane extraction was used for plasma, and for brain homogenate the hexane extract was further purified by solid-phase extraction. The determination limit was ca. 3 ng/ml for both plasma (0.5 ml) and 10% (w/v) brain homogenate (1 ml). The method was applied to the determination of I in plasma and brain samples of experimental animals.     

Synchronous Fluorescence Spectroscopy for the Detection and Characterization of Cervical Cancers In Vitro

The objective of this study was to assess the diagnostic potential of synchronous fluorescence (SF) spectroscopy (SFS) technique for the detection and characterization of normal and different malignancy stages of moderately differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous cell carcinoma (PDSCC) cervical tissues. SF spectra were measured from 45 biopsies from 30 patients in vitro . Characteristic, highly resolved peaks and significant spectral differences between normal and MDSCC, PDSCC cervical tissues were obtained. Nine potential ratios were calculated and used as input variables for a discriminant analysis across different groups. The potentiality of the SFS technique was estimated by two discriminant analyses. Discriminant analysis I performed across normal and abnormal (including MDSCC and PDSCC) cervical tissues classified as 100% both original and the cross-validated grouped cases. In discriminant analysis II performed across the three groups, normal, MDSCC and PDSCC, 100% of both original and the cross-validated grouped cases were correctly classified. Using the SFS technique, one can obtain all the key biochemical markers such as tryptophan, collagen, hemoglobin, reduced form of nicotinamide adenine dinucleotide and flavin adenine dinucleotide in a single scan and hence they can be targeted as tumor markers in the detection of normal from abnormal cervical tissues.     

A sensitive and selective spectrophotometric estimation of catechol derivatives in pharmaceutical preparations

A sensitive and simple spectrophotometric method for the estimation of catechol and its derivatives like dopamine hydrochloride (DPH), levodopa (LDP), methyldopa (MDP) and adrenaline hydrochloride (ADH) in both pure form and in pharmaceutical formulation, is described. The method is based on the interaction of diazotised sulphanilamide (DSA) with catechol derivatives in the presence of molybdate ions in acidic medium. Absorbance of the resulting red coloured product is measured at 490 nm for pyrocatechol (PCL) and at 500 nm for other catechol derivatives. The colour reaction is stable for 24–30 h. Under optimal conditions, Beer's Law range for pyrocatechol was found to be between 0.04 and 2.4 (R.S.D.=0.78%), for DPH was 0.02–2.8 (R.S.D.=0.98%) for LDP was 0.1–2.8 (R.S.D.=1.21%) for MDP was 0.5–7 (R.S.D.=1.41%) and for ADH was 0.5–7 (R.S.D.=1.58%). The method is highly reproducible and specific for these selected catechol derivatives. The common excipients used as additives do not interfere in the proposed method. Analytical data for the determination of the pure compound is presented together with the application of the proposed method to the analysis of some pharmaceutical formulations. The results compare favourably with those of official and reported methods.     

Simultaneous determination of the camptothecin analogue CPT-11 and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in cancer patients.

CPT-11 (I; 7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin) is a new anticancer agent currently under clinical development. A sensitive high-performance liquid chromatographic assay suitable for the simultaneous determination of I and its active metabolite SN-38 (II) in human plasma, and their preliminary clinical pharmacokinetics, are described. Plasma samples were processed using a solid-phase (C18) extraction step allowing mean recoveries of I, II and the internal standard camptothecin (III) of 84, 99 and 72%, respectively. The extracts were chromatographed on a C18 reversed-phase column with a mobile phase composed of acetonitrile, phosphate buffer and heptanesulphonic acid, with fluorescence detection. The calibration graphs were linear over a wide range of concentrations (1 ng/ml-10 micrograms/ml), and the lower limit of determination was 1 ng/ml for both I and II. The method showed good precision: the within-day relative standard deviation (R.S.D.) (5-1000 ng/ml) was 13.0% (range 4.9-19.4%) for I and 12.8% (6.7-19.1%) for II; the between-day R.S.D. (5-10,000 ng/ml was 7.9% (5.4-17.5%) for I and 9.7% (3.5-15.1%) for II. Using this assay, plasma pharmacokinetics of both I and II were simultaneously determined in three patients receiving 100 mg/m2 I as a 30-min intravenous infusion. The mean peak plasma concentration of I at the end of the intravenous infusion was 2400 +/- 285 ng/ml (mean +/- standard error of the mean). Plasma decay was triphasic with half-lives alpha, beta and gamma of 5.4 +/- 1.8 min, 2.5 +/- 0.5 h and 20.2 +/- 4.6 h, respectively. The volume of distribution at steady state was 105 +/- 15 l/m2, and the total body clearance was 12.5 +/- 1.9 l/h.m2. The maximum concentrations of the active metabolite II reached 36 +/- 11 ng/ml.     

Synthesis and characterization of a novel electrochromic aromatic polyamide from AB‐type triphenylamine‐based monomer

A new triphenylamine‐based polyamide I was prepared by direct polycondensation of AB‐type monomer, 4‐amino‐4′‐carboxy‐4″‐methoxytriphenylamine ( 4 ), in the presence of triphenyl phosphite and pyridine as condensation agents. The obtained polyamide I showed excellent solubility in aprotic polar solvents such as NMP, DMAc, DMF, and DMSO and could be cast into transparent film with weight‐average molecular weight (M_w = 63,400) and polydispersity index (PDI = 1.79). The polyamide I exhibited good thermal stability with relatively high glass‐transition temperature (282 °C), 10% weight‐loss temperature above 470 °C under a nitrogen atmosphere, and char yield at 800 °C in nitrogen higher than 64%. It also showed maximum ultraviolet‐visible absorption at 362 nm and exhibited fluorescence emission maxima at 493 nm in NMP solution with fluorescence quantum yield 4.4%. Cyclic voltammogram of polyamide I film cast onto an indium tin oxide coated glass substrate exhibited one oxidative redox couple at 0.72 V (oxidation onset potential) versus Ag/AgCl in acetonitrile solution and revealed good stability of the electrochromic characteristic with a color change from colorless to green at applied potentials ranging from 0.00 to 1.10 V. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1988–2001, 2009     

Fluorescent and colorimetric immunoassay of nuclear matrix protein 22 enhanced by porous Pd nanoparticles

A new modified ELISA enhanced by porous Pd nanoparticles for colorimetric and fluorescence dual-modal immunoassay of nuclear matrix protein 22 has been demonstrated. Benefited from different signalreadout and independent signal amplified mechanism, the improved ELISA will afford more reliable detection performance, which can bring high promising for clinical diagnosis.     

Study of the adsorption reactions of thiophene on Cu(I)/HY-Al2O3 by Fourier transform infrared and temperature-programmed desorption: adsorption, desorption, and sorbent regeneration mechanisms

This work mainly involved the investigation of the adsorption of thiophene on Cu(I)-supported HY-Al(2)O(3). It demonstrated a high sulfur capacity of 10 mg sulfur/g sorbent when the HY/Al(2)O(3) mass ratio was 3, loaded with 12% copper, calcined at 550 °C, and tested at ambient temperature. In situ Fourier transform infrared (FTIR) and temperature-programmed desorption (TPD) results indicated that the adsorption mechanisms on Cu(I)/HY-Al(2)O(3) primarily were π-complexation and sulfur-adsorbent (S-M; σ) bonds. Pyridine-FTIR showed the total weak Lewis acid contribution to the Cu(I)/HY-Al(2)O(3) adsorption desulfurization performance.     

Hypericin and hypocrellin induced apoptosis in human mucosal carcinoma cells.

Potent photosensitizers hypocrellin A (HA), hypocrellin B (HB) and hypericin (HY) are lipid-soluble perylquinone derivatives of the genus Hypericum and have a strong photodynamic effect on tumors and viruses. However, the mechanisms of tumor cell death induced by HA, HB and HY are still unclear. Moreover, no reports have mentioned cell apoptosis induced by HA, HB and HY in human nasopharyngeal carcinoma (NPC) and other mucosal cells. In this study, we attempt to clarify the photodynamic effects of HA, HB and HY compounds in poorly differentiated (CNE2) and moderately differentiated (TW0-1) human NPC cells as well as human mucosal colon and bladder cells. Using these cell lines we investigated few hallmarks of apoptotic commitments in a drug dose dependent manner. Tumor cells photo-activated with HA, HB and HY showed cell size shrinkage and an increase in the sub-diploid DNA content. A loss of membrane phospholipid asymmetry associated with apoptosis was induced by all tumor cell lines as evidenced by the externalization of phosphatidylserine. Under apoptotic conditions, Western blot analysis of poly(ADP-ribose) polymerase, a caspases substrate, showed the classical cleavage pattern (116 to 85 kDa) associated with apoptosis in HA, HB and HY-treated cell lysates. In addition, 85 kDa cleaved product was blocked by the tetrapepdide caspase inhibitors such as DEVD-CHO or z-VAD-fmk. Both inhibitors protect tumor cells from apoptosis. These results demonstrate that tumor cell death induced by HA, HB and HY is mediated by caspase proteases. This study also identifies HB as a more potent and promising photosensitizer for the treatment of mucosal cancer cells.