Accelerated synthesis of phthalimide derivatives: Intrinsic reactivity of diamines towards phthalic anhydride evaluated by paper spray ionization mass spectrometry.

RATIONALE: Paper spray (PS) is a simple and innovative ambient ionization technique for mass spectrometry (MS) analysis. Under PS-MS conditions, chemical reactions, which usually occur slowly on a bulk scale, are accelerated. Moreover, the formation of products and transient species can be easily monitored. In this manuscript, reactions between phthalic anhydride and diamines were conducted and monitored using a PS-MS platform. The reaction products (phthalimides) have many pharmaceutical applications, but their traditional syntheses can take hours under reflux, requiring laborious purification steps. METHODS: In situ reactions were performed by dropping methanolic solutions of phthalic anhydride and diamines on a triangular paper. The analyses were achieved by positioning the triangle tip in front of the mass spectrometer entrance, whereas a metal clip was attached to the triangle base. After adding methanol to the paper, a high voltage was applied across the metal clip, and the mass spectra were acquired. RESULTS: The intrinsic reactivity of alkyl and aromatic diamines was evaluated. The carbon chain remarkably influenced the reactivity of aliphatic diamines. For aryl diamines, the ortho isomer was the most reactive. Moreover, for aryl amines with electron-withdrawing substituents, no reaction was noticed. CONCLUSIONS: Taking advantage of the unique characteristics of PS-MS, it was possible to investigate the intrinsic reactivity of model alkyl (ethylene versus propylene) and aryl (o-phenylene versus m-phenylene and p-phenylene) diamines towards phthalic anhydride. Some crucial parameters that affect the intrinsic reactivity of organic molecules, such as isomerism, intramolecular interaction, and conformation, were easily explored.

Preparation and properties of novel bio-based epoxy resin thermosets from lignin oligomers and cardanol.

A series of lignin-based epoxy resins (LEPs) were prepared by the reaction of epichlorohydrin with lignin oligomers derived from partial reductive depolymerization of lignin. To overcome the high viscosity and brittleness defects in practical applications, the LEPs were blended with renewable epoxied cardanol glycidyl ether (ECGE) and then cured with methyltetrahydrophthalic anhydride (MeTHPA) to form high-performance epoxy thermosets. The effects of degree of lignin depolymerization, chemical composition of lignin oligomers and dosage of ECGE on thermal and mechanical properties of the cured products were investigated. The LEP/MeTHPA thermosets exhibited good thermal and mechanical properties. Especially, by separating monomer-rich fractions from lignin oligomers, the thermal and mechanical properties of the cured product were improved obviously. Notably, the incorporation of ECGE also possessed a positive effect on reinforcing and toughening the cured products. With 20 wt% ECGE loadings, the tensile, flexural and impact strength of the cured product reached the maximum value of 77 MPa, 115 MPa and 14 kJ/m2, respectively, which were equivalent to the commercial bisphenol A epoxy resins thermosets. These findings indicated that the novel bio-based epoxy resins from lignin oligomers and cardanol could be utilized as renewable alternatives for BPA epoxy resins.

Chemical Modifications Induced by Phthalic Anhydride, a Respiratory Sensitizer, in Reconstructed Human Epidermis: A Combined HRMAS NMR and LC-MS/MS Proteomic Approach.

Chemical skin and respiratory allergies are becoming a major health problem. To date our knowledge on the process of protein haptenation is still limited and mainly derived from studies performed in solution using model nucleophiles. In order to better understand chemical interactions between chemical allergens and the skin, we have investigated the reactivity of phthalic anhydride 1 (PA), a chemical respiratory sensitizer, toward reconstructed human epidermis (RHE). This study was performed using a new approach combining HRMAS NMR to investigate the in situ chemical reactivity and LC-MS/MS to identify modified epidermal proteins. In RHE, the reaction of PA appeared to be quite fast and the major product formed was phthalic acid. Two amide type adducts on lysine residues were observed and after 8h of incubation, we also observed the formation of an imide type cyclized adducts with lysine. In parallel, RHE samples topically exposed to phthalic anhydride (13C)-1 were analyzed using the shotgun proteomics method. Thus, 948 different proteins were extracted and identified, 135 of which being modified by PA, i.e., 14.2% of the extracted proteome. A total of 211 amino acids were modified by PA and validated by fragmentation spectra. We thus identified 154 modified lysines, 22 modified histidines, 30 modified tyrosines, and 5 modified arginines. The rate of modified residues, as a proportion of the total number of modifiable nucleophilic residues in RHE, was rather low (1%). At the protein level, modified proteins were mainly type I and type II keratins and other proteins which are abundant in the epidermis such as protein S100A, Caspase 14, annexin A2, serpin B3, fatty-acid binding protein 5, histone H2, H3, H4, etc. However, the most modified protein, mainly on histidine residues, was filaggrin, a protein that is of low abundance (0.0266 mol %) and rich in histidine.

Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-n-Butylidenephthalide.

Phthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtaining 3-butyl-3-hydroxyphthalide, which is the metabolite formulated during mammalian metabolism of 3-n-butylidenephthalide. We performed transformations using 10 strains of fungi, five of which efficiently produced 3-butyl-3-hydroxyphthalide. The product yield, determined by high-performance liquid chromatography, reached 97.6% when Aspergillus candidus AM 386 was used as the biocatalyst. Increasing the scale of the process resulted in isolation yields of 29-45% after purification via reversed-phase thin layer chromatography, depending on the strain of the microorganism used. We proposed different mechanisms for product formation; however, hydration of 3-n-butylidenephthalide seems to be the most probable. Additionally, all phthalides were tested against clinical strains of Candida albicans using the microdilution method. Two phthalides showed a minimum inhibitory concentration, required to inhibit the growth of 50% of organisms, below 50 µg/mL. The 3-n-butylidenephthalide metabolite was generally inactive, and this feature in combination with its low lipophilicity suggests its involvement in the detoxification pathway. The log P value of tested compounds was in the range of 2.09-3.38.

Positively Charged Nanoparticle Delivery of n-Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the second and sixth leading cause of cancer death in men and woman in 185 countries statistics, respectively. n-Butylidenephthalide (BP) has shown anti-HCC activity, but it also has an unstable structure that decreases its potential antitumor activity. The aim of this study was to investigate the cell uptake, activity protection, and antitumor mechanism of BP encapsulated in the novel liposome LPPC in HCC cells. BP/LPPC exhibited higher cell uptake and cytotoxicity than BP alone, and combined with clinical drug etoposide (VP-16), BP/LPPC showed a synergistic effect against HCC cells. Additionally, BP/LPPC increased cell cycle regulators (p53, p-p53, and p21) and decreased cell cycle-related proteins (Rb, p-Rb, CDK4, and cyclin D1), leading to cell cycle arrest at the G0/G1 phase in HCC cells. BP/LPPC induced cell apoptosis through activation of both the extrinsic (Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways and activated the caspase cascade to trigger HCC cell death. In conclusion, the LPPC complex improved the antitumor activity of BP in terms of cytotoxicity, cell cycle regulation and cell apoptosis, and BP/LPPC synergistically inhibited cell growth during combination treatment with VP-16 in HCC cells. Therefore, BP/LPPC is potentially a good candidate for clinical drug development or for use as an adjuvant for clinical drugs as a combination therapy for hepatocellular carcinoma.

Identification of the metabolites of n-butylidenephthalide in rat and human liver microsomes by liquid chromatography-high-resolution mass spectrometry.

n-Butylidenephthalide (NBDP) is one of the bioactive constituents originally isolated from Ligusticum chuanxiong Hort. The aim of this study was to study the metabolic profiles of NBDP in rat and human liver microsomes. NBDP was individually incubated with liver microsomes of rat and human at 37°C for 1 h and the samples incubated were analyzed by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry. The identities of the metabolites were identified by accurate masses, product ions and retention times. Under the current conditions, a total of 14 metabolites were detected and identified. M12, M13 and M14 were biosynthesized and unambiguously characterized by nuclear magnetic resonance spectroscopy. All the metabolites can be detected in rat liver microsomes, whereas in human liver microsomes, M1, M3, M4, M5, M6 and M7 were not detected. Our results demonstrated that the metabolic pathways of NBDP included hydroxylation, hydration, hydrolysis and glutathione conjugation. This study provides an overview of the metabolic profiles of NBDP in vitro, which is helpful to understand the action of this compound.

Phthalic anhydride esterified chicha gum: characterization and antibacterial activity.

The objective of this research was to modify chicha gum with phthalic anhydride to obtain a new biologically active material. The chemical modification of the gum structure was proven through FTIR, elemental analysis, XRD, TG, and DSC. The derived materials demonstrated excellent inhibitory effect against P. aeruginosa and K. pneumoniae species (rating 100% inhibition) and could also inhibit Escherichia coli growth. The best antimicrobial activity observed for the derivatives suggests that chicha gum hydrophobization due to the addition of phthalic groups improved the interaction of these derivatives with bacterial cell wall components. On the other hand, the derivatives increased CC50 in macrophages but did not present acute toxicity or hemolytic activity, indicating that they are promising for use in prophylaxis or treatment of infections caused by Gram-negative bacteria.

Safety Assessment of Trimellitic Anhydride Copolymers as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 6 trimellitic anhydride copolymers as used in cosmetics. These ingredients are related as copolymers in that they all share trimellitic anhydride (ie, 1,2,4-benzenetricarboxylic acid anhydride) as a monomer, are reported to function as film formers in cosmetics, and are reported to be primarily used in nail products. Very limited safety data were available or submitted. The Panel concluded that Adipic Acid/Neopentyl Glycol/Trimellitic Anhydride Copolymer and Phthalic Anhydride/Trimellitic Anhydride/Glycols Copolymer are safe in nail product formulations in the present practices of use and concentration, but the data are insufficient to make a determination of safety on the use of these 2 ingredients in all other types of cosmetic formulations. The Panel also concluded that the available data are insufficient to make a determination that the remaining trimellitic anhydride copolymers are safe for use in cosmetic formulations.

Antitumor Effects of N-Butylidenephthalide Encapsulated in Lipopolyplexs in Colorectal Cancer Cells.

Colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related death in the world. N-Butylidenephthalide (BP), a natural compound, inhibits several cancers, such as hepatoma, brain tumor and colon cancer. However, due to the unstable structure, the activity of BP is quickly lost after dissolution in an aqueous solution. A polycationic liposomal polyethylenimine and polyethylene glycol complex (LPPC), a new drug carrier, encapsulates both hydrophobic and hydrophilic compounds, maintains the activity of the compound, and increases uptake of cancer cells. The purpose of this study is to investigate the antitumor effects and protection of BP encapsulated in LPPC in CRC cells. The LPPC encapsulation protected BP activity, increased the cytotoxicity of BP and enhanced cell uptake through clathrin-mediated endocytosis. Moreover, the BP/LPPC-regulated the expression of the p21 protein and cell cycle-related proteins (CDK4, Cyclin B1 and Cyclin D1), resulting in an increase in the population of cells in the G0/G1 and subG1 phases. BP/LPPC induced cell apoptosis by activating the extrinsic (Fas, Fas-L and Caspase-8) and intrinsic (Bax and Caspase-9) apoptosis pathways. Additionally, BP/LPPC combined with 5-FU synergistically inhibited the growth of HT-29 cells. In conclusion, LPPC enhanced the antitumor activity and cellular uptake of BP, and the BP/LPPC complex induced cell cycle arrest and apoptosis, thereby causing death. These findings suggest the putative use of BP/LPPC as an adjuvant cytotoxic agent for colorectal cancer.

Antiviral, Antimicrobial and Antibiofilm Activity of Selenoesters and Selenoanhydrides.

Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications.

Mechanism of ß2AR regulation by an intracellular positive allosteric modulator.

Drugs targeting the orthosteric, primary binding site of G protein-coupled receptors are the most common therapeutics. Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. We report the crystal structure of the prototypic ß2-adrenergic receptor in complex with an orthosteric agonist and compound-6FA, a positive allosteric modulator of this receptor. It binds on the receptor's inner surface in a pocket created by intracellular loop 2 and transmembrane segments 3 and 4, stabilizing the loop in an α-helical conformation required to engage the G protein. Structural comparison explains the selectivity of the compound for ß2- over the ß1-adrenergic receptor. Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs.

Integration of PEG 400 into a self-nanoemulsifying drug delivery system improves drug loading capacity and nasal mucosa permeability and prolongs the survival of rats with malignant brain tumors.

Introduction: Kolliphor® EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity. Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor® HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.

Synthesis and characterization of novel trimellitic anhydride isothiocyanate-cross linked chitosan hydrogels modified with multi-walled carbon nanotubes for enhancement of antimicrobial activity.

Novel trimellitic anhydride isothiocyanate was successfully synthesized and utilized in various concentrations to obtain four novel cross linked chitosan hydrogels H1-H4. Three multi-walled carbon nanotube (MWCNT) biocomposites based on H1 were also prepared. Their structures were proven by elemental analysis, FTIR, XRD, SEM and TEM. They were found to be pH- and temperature-responsive materials. Their swell abilities appreciably depend on their cross linking moiety contents and MWCNTs concentration. They are more potent against Bacillis subtilis, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Geotrichum candidum, Candida albicans, Aspergillus fumigatus, and Syncephalastrum racemosum than chitosan as judged by their greater inhibition zone diameters and their lower minimum inhibitory concentration (MIC) values. Their antimicrobial activities increased with increasing their cross linking moiety contents. They showed a better potency against Gram-positive than Gram-negative bacteria. The hydrogel H4 and H1/MWCNT composites have comparable or even higher activities than the reference bactericides or fungicides against some of tested microbes. Thus, combination between chitosan and the functionalized groups of the incorporated cross linker as well as MWCNTs in one system has efficiently improved the chitosan features. It is a good way for attaining adequate systems as antimicrobial agents that can be taken as promising candidates in biomedical fields.

Riboflavin immobilized Fe3O4 magnetic nanoparticles carried with n-butylidenephthalide as targeting-based anticancer agents.

n-Butylidenephthalide (BP) is a potential anti-cancer drug, which can be extracted from Angelica sinensis (Danggui). Previous reports have shown the effectiveness of BP in treating cancer diseases. However, BP has no targeting capacity towards specific cancer cells. To improve treatment efficiency and reduce the dose of BP used in cancer treatment, targeting-based approaches should be developed. In the present study, we used riboflavin-5'-phosphate (RFMP) immobilized iron oxide magnetic nanoparticles (Fe3O4 MNPs) as carriers for BP to treat cancer cell lines derived from liver, prostate and breast. These model cancer cells overexpress riboflavin receptors on their cell membrane and are also sensitive to BP treatment. Thus, BP-binding free RFMP on MNPs can be used as probes to target these model cells, whereas BP can be readily released on target cancer cells. Cell viability was twofold lower by using Fe3O4@RFMP MNPs immobilized with BP than that achieved by using free-form BP at a similar amount. Moreover, BP-Fe3O4@RFMP MNPs have no apparent harmful effects on non-target cells. In addition, we evaluated the level of cysteine-aspartic acid protease 3 (caspase 3) in the resultant cell lysate obtained after treatment by BP-Fe3O4@RFMP MNPs to demonstrate that apoptosis is mainly involved in the growth inhibition of target cells.

Development of a low-cost electrochemical sensor based on babassu mesocarp (Orbignya phalerata) immobilized on a flexible gold electrode for applications in sensors for 5-fluorouracil chemotherapeutics.

There are increasing concerns regarding the risks arising from the contamination of manipulators of antineoplastic drugs promoted by occupational exposure or even in the dosage of drugs. The present work proposes the use of an electrochemical sensor based on a biopolymer extracted from the babassu coconut (Orbignya phalerata) for the determination of an antineoplastic 5-fluorouracil (5-FU) drug as an alternative for the monitoring of these drugs. In order to reduce the cost of this sensor, a flexible gold electrode (FEAu) is proposed. The surface modification of FEAu was performed with the deposition of a casting film of the biopolymer extracted from the babassu mesocarp (BM) and modified with phthalic anhydride (BMPA). The electrochemical activity of the modified electrode was characterized by cyclic voltammetry (CV), and its morphology was observed by atomic force microscopy (AFM). The FEAu/BMPA showed a high sensitivity (8.8 µA/µmol/L) and low limit of detection (0.34 µmol/L) for the 5-FU drug in an acid medium. Electrochemical sensors developed from the babassu mesocarp may be a viable alternative for the monitoring of the 5-FU antineoplastic in pharmaceutical formulations, because in addition to being sensitive to this drug, they are constructed of a natural polymer, renewable, and abundant in nature. Graphical abstract ᅟ.

Antitumor Effect of n-Butylidenephthalide Encapsulated on B16/F10 Melanoma Cells In Vitro with a Polycationic Liposome Containing PEI and Polyethylene Glycol Complex.

Advanced melanoma can metastasize to distal organs from the skin and yield an aggressive disease and poor prognosis even after treatment with chemotherapeutic agents. The compound n-Butylidenephthalide (BP) is isolated from Angelica sinensis, which is used to treat anemia and gynecological dysfunction in traditional Chinese medicine. Studies have indicated that BP can inhibit cancers, including brain, lung, prostate, liver, and colon cancers. However, because BP is a natural hydrophobic compound, it is quickly metabolized by the liver within 24 h, and thus has limited potential for development in cancer therapy. This study investigated the anticancer mechanisms of BP through encapsulation with a novel polycationic liposome containing polyethylenimine (PEI) and polyethylene glycol complex (LPPC) in melanoma cells. The results demonstrated that BP/LPPC had higher cytotoxicity than BP alone and induced cell cycle arrest at the G0/G1 phase in B16/F10 melanoma cells. The BP/LPPC-treated cell indicated an increase in subG1 percentage and TUNEL positive apoptotic morphology through induction of extrinsic and intrinsic apoptosis pathways. The combination of BP and LPPC and clinical drug 5-Fluorouracil had a greater synergistic inhibition effect than did a single drug. Moreover, LPPC encapsulation improved the uptake of BP values through enhancement of cell endocytosis and maintained BP cytotoxicity activity within 24 h. In conclusion, BP/LPPC can inhibit growth of melanoma cells and induce cell arrest and apoptosis, indicating that BP/LPPC has great potential for development of melanoma therapy agents.

Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition.

BACKGROUND/AIMS: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. METHODS: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan's National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. RESULTS: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. CONCLUSION: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

Intrinsically fluorescent and highly functionalized polymer nanoparticles as probes for the detection of zinc and pyrophosphate ions in rabbit serum samples.

Intrinsically fluorescent polymer nanoparticles (F-PNPs) were synthetized from 2-hydroxy-5-methylisophthalaldehyde and melamine by solvothermal method. F-PNPs can emit strong yellow green fluorescence at 542 nm without the conjugation to any external fluorescent agent and surface modification. Owing to the abundant amino and hydroxyl groups on their surface, the F-PNPs possess multiple binding sites, good biocompatibility and excellent water-solubility. Addition of Zn2+ to the F-PNPs solution resulted in a blue shift (Δλ=40 nm) with obvious enhancement in the fluorescence intensity at 502 nm; while there was negligible change in the presence of other metal ions. The subsequent treatment with pyrophosphate (PPi) can cause fluorescence recovery of F-PNPs by pulling the Zn2+ out of the coordination cavity of F-PNPs-Zn2+ nanocomposites. No interference was observed from other anions and nucleotides, making the F-PNPs-Zn2+ ensembles highly sensitive and selective nanoprobes for PPi. The detection limit is 2.75 × 10-8 M/L and 7.63 × 10-8 M/L for Zn2+ and PPi, respectively. The proposed nanoprobes were then used for detecting the recovery of Zn2+ and PPi in rabbit serum samples, which were found to be 99.4-104.2% and 98.6-104.7%, respectively. The present strategy for the fabrication of nanoparticles may offer a new sight for the preparation of polymer nanostructures. The F-FNPs based probes can provide an accurate method for the detection of Zn2+ and PPi in serum samples.

Potential of Cellulose Functionalized with Carboxylic Acid as Biosorbent for the Removal of Cationic Dyes in Aqueous Solution.

In the last decade, adsorption has been used to minimize the pollution caused by dyes, which represents a serious environmental problem. In this context, this work reports the preparation of phthalic anhydride-modified cellulose (PhCel), through the reaction of cellulose (Cel) with phthalic anhydride (Ph). The efficiency of the reaction was observed by elemental analysis, Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and thermogravimetry/derivative thermogravimetry (TG/DTG). The adsorbent matrix (Cel and PhCel) was used in the removal of crystal violet (CV) and methylene blue (MB) dyes in aqueous medium. In the kinetic study, the experimental data obtained had the best fit to the pseudo-first-order model. In general, the isotherms obtained at different temperatures had a best fit to the model proposed by Langmuir, and the CV and MB adsorption process in adsorbent matrixes can be favored strictly by hydrogen bonds and/or electrostatic interactions for Cel and electrostatic interactions for PhCel.

Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human Breast Cancer Cells.

N-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine, Radix Angelica Sinensis (danggui), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying mechanism of action in human breast cancer cells. BP induces apoptosis in breast cancer cells, which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was detected by western blot. In addition, BP-induced G2/M arrest was examined by flow cytometry and the expression levels of the G2/M regulatory protein were detected by western blot. BP also suppresses the migration and invasion of breast cancer cells, which was tested by wound healing and the matrigel invasion assay; the involvement of EMT-related gene expressions was detected by real-time PCR. Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was measured by the colony formation assay and comet assay, where the foci of γ-H2AX after radiation significantly increased in BP pretreated cells and was evidenced by immunocytochemistry staining and western blot. The homologous recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment. These results indicate that BP might be a potential chemotherapeutic and radiosensitizing agent for breast cancer therapy.