ß-Cyclodextrin and diatomite immobilized in sodium alginate biosorbent for selective uranium(VI) adsorption in aqueous solution.

The separation and enrichment of uranium from various resources such as seawater is of great significance to the sustainable development of nuclear energy. Therefore, there is an urgent need to develop an adsorbent with low cost and easy availability, simple preparation process, and environment friendly. In this work, we used inexpensive natural polymer material (sodium alginate) and natural adsorbents (ß-cyclodextrin and diatomite) to prepare a novel biosorbent ß-cyclodextrin/sodium alginate/diatomite (CSD) hydrogel beads for uranium adsorption by a simple method. The results of FTIR, XRD, SEM, EDX and XPS characterization proved that the CSD were prepared. Static adsorption experiments showed that pH, contact time, initial concentration of U(VI) and temperature has significant impact on the adsorption capacity of CSD. Adsorption fitted the pseudo-second-order kinetic model and Langmuir model and the adsorption mechanism is chemical adsorption. In the presence of other metal ions (Cu2+, Mg2+, Ca2+, Na+, K+), CSD has obvious selectivity for uranium(VI) adsorption. In addition, the elution and reusability studies show that CSD has excellent reusability. Overall, CSD is an inexpensive, green preparation, efficient, and environment friendly biosorbent with obvious selectivity for U(VI). It has potential application in U(VI) enrichment from seawater or salt lake water.

Graphene oxide encapsulated polyvinyl alcohol/sodium alginate hydrogel microspheres for Cu (II) and U (VI) removal.

In this work, a novel sodium alginate (SA)/polyvinyl alcohol (PVA)/graphene oxide (GO) hydrogel microspheres were prepared by a simple method. Sodium alginate was physically crosslinked by Ca2+; GO was encapsulated into the composite to strengthen the hydrogels; PVA played a significant role in well dispersing of GO in SA. The SA/PVA/GO (SPG) hydrogels were employed as an efficient adsorbent for removal of Cu (II) and U (VI) from aqueous solution. Batch experiments with the subject of the pH, initial metal ion concentration, competing ions and contact time were investigated. Structure characterization was successfully conducted by FTIR, SEM, EDX, BET and XPS. Furthermore, the sorption kinetics of Cu2+ and UO22+ followed pseudo-second order model and exhibited 3-stage intraparticle diffusion model. Equilibrium data were best described by Langmuir model and the obtained maximum adsorption capacities of SPG hydrogel microspheres for Cu2+ and UO22+ were 247.16 and 403.78 mg/g, respectively. The difference in adsorption capacity can be confirmed by the percentage of elements in EDX spectra and the intension of peak of elements in XPS spectra. The SPG sorbent exhibited excellent reusability after 5 adsorption-desorption cycles. All results suggested that the prepared adsorbents could be considered as effective and promising materials for removal of Cu (II) and U (VI) in wastewater.

Modification of chitosan/calcium alginate/Fe3O4 hydrogel microsphere for enhancement of Cu(II) adsorption.

Copper in drinking water causes a significant environmental problem. Composite material based on alginate hydrogel has been gaining attention in the field of Cu(II) adsorption. However, alginate-based hydrogel exhibits poor mechanical property and relative low adsorption capacity which limit their application. The present study is devoted to the modification of chitosan/calcium alginate/Fe3O4 (CAF) hydrogel microsphere by NaOH solution for enhancement of Cu(II) adsorption. Results reveal that modification of CAF via NaOH solution significantly improves the mechanical strength and Cu2+ adsorption capacity of pristine materials. FTIR and XRD analysis confirms that CAF and newly prepared materials (NACAF) are successfully prepared. SEM and EDX are employed to analyze the surface morphology and elemental composition, respectively, both before and after their loading with Cu2+. XPS study demonstrates adsorption mechanism is based on chelation and ion-exchange. Compressive stress-strain curves demonstrate NACAF has better mechanical performance than CAF. The adsorption kinetics of the two adsorbents follow a pseudo-second-order model. The equilibrium data were best described by Langmuir isotherm model, and the estimated maximum equilibrium sorption capacity, q m,is 261.31 mg/g for the NACAF, which is larger than that of CAF (145.39 mg/g). Hence, NACAF shows excellent mechanical strength and high sorption capacity for Cu2+. It has great potential for Cu(II) removal in aqueous solutions.

Encapsulating Fe3O4 into calcium alginate coated chitosan hydrochloride hydrogel beads for removal of Cu (II) and U (VI) from aqueous solutions.

The aim of this work was to study the removal of Cu (II) and U (VI) ions from aqueous solutions by encapsulating magnetic Fe3O4 nanoparticles into calcium alginate coated chitosan hydrochloride (CCM) hydrogel beads. ATR-FTIR and XRD analysis data indicated that the CCM composites were successfully prepared. SEM images and EDX spectra showed that Cu2+ and UO22+ ions were adhered onto sorbents. Adsorption properties for removal of both copper and uranium ions under various experimental conditions were investigated. Kinetic data and sorption equilibrium isotherms were also conducted in batch process. The sorption kinetic analysis revealed that sorption of Cu (II) and U (VI) followed the pseudo-second-order model well and exhibited 3-stage intraparticle diffusion model during the whole sorption process. Equilibrium data were best described by Langmuir model, and the CCM composite hydrogel beads showed the estimated maximum adsorption capacity 143.276mg/g and 392.692mg/g for Cu (II) and U (VI), respectively. The CCM adsorbent exhibited excellent reusability for five cycles use without significant changes in the adsorption capacity and structural stability. The results demonstrated that CCM can be an effective and promising sorbent for Cu (II) and U (VI) ions in wastewater.

Preparation of a novel polyacrylic acid and chitosan interpenetrating network hydrogel for removal of U(vi) from aqueous solutions.

A clean and simple method has been developed for preparation of interpenetrating polymer networks using polyacrylic acid (PAA) and chitosan (CS) for extraction of uranium from polluted water. The peak of Fourier transform infrared spectroscopy (FTIR) occurred at 928 cm-1 indicating combination of uranium and PAA/CS. The energy dispersive X-ray (EDX) and the scanning electron microscope (SEM) studies illustrated the formation of a crosslinking structure and excellent binding ability of uranium on PAA/CS. The maximum adsorption capacity was 289.6 mg g-1 calculated using the equation of the Langmuir model. The adsorption capacity reached a plateau at pH 4 and the sorption process fits the pseudo-second-order model well. The PAA/CS composite has stability of reuse, with the adsorbent capacity decreasing slowly with increasing usage frequency. The experimental results confirm that the PAA/CS hydrogel could be a novel alternative for highly efficient removal of uranium from wastewater.

Oxidative removal of phenol by HRP-immobilized beads and its environmental toxicology assessment.

Horseradish peroxidase shows potential biological and environmental applications on the removal of phenolic compounds. In the present study, the HRP-immobilized beads were synthesized to detect the efficiency of the removal of phenol at optimum pH and H2O2 concentration. Comparative in vitro cytotoxicity of phenol/treated solutions were evaluated in HeLa, HepG2 and mcf-7 cells by using MTT method along with flow cytometry study for cell viability and cell cycle distributions. The results showed that the toxicity of phenol solutions were greatly reduced after treated by HRP-immobilized beads, and phenol could lead to deactivate of cells in the S phase and preventing them from going into the G2/M checkpoint. In addition, molecular docking study showed that phenol was a valid inhibitor for the cyclin E in the cell cycle and cell metabolism. Thereby, we established a suitable strategy with promising application for efficient harmless removal of phenol, which significantly decreased the cytotoxic impacts of phenol.

Synthesis and Biological Evaluation of Novel Ursolic acid Derivatives as Potential Anticancer Prodrugs.

Ursolic acid (UA) is a natural product which has been shown to possess a wide range of pharmacological activities, in particular those with anticancer activity. In this study, 13 novel ursolic acid derivatives were designed and synthesized in an attempt to further improve compound potency. The structures of the newly synthesized compounds were confirmed using mass spectrometry, infrared spectroscopy, and (1) H NMR. The ability of the UA derivatives to inhibit cell growth was assayed against both various tumor cell lines and a non-pathogenic cell line, HELF. Analysis of theoretical toxicity risks for all derivatives was performed using OSIRIS and indicated that the majority of compounds would present moderate to low risks. Pharmacological results indicated that the majority of the derivatives were more potent growth inhibitors than UA. In particular, 5b demonstrated IC50 values ranging from 4.09 ± 0.27 to 7.78 ± 0.43 µm against 12 different tumor cell lines. Flow cytometry analysis indicated that 5b induced G0/G1 arrest in three of these cell lines. These results were validated by structural docking studies, which confirmed that UA could bind to cyclins D1 (Cyc D1) and cyclin-dependent kinases (CDK6), the key regulators of G0/G1 transition in cell cycle, while the piperazine moiety of 5b could bind with glucokinase (GK), glucose transporter 1 (GLUT1), and ATPase, which are the main proteins involved in cancer cell metabolism. Acridine orange/ethidium bromide staining confirmed that 5b was capable of inducing apoptosis and decreasing cell viability in a dose-dependent manner.

A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis.

Here we showed that ursolic acid (UA), a pentacyclic triterpene natural product, and its novel prodrug derivative US597 suppressed cancer cells adhesion, invasion and migration. This effect was accompanied by inhibition of focal adhesion signaling pathway including alterations in ICAM-1, VCAM-1, E-selectin, P-selectin, integrin α6ß1, FAK, Src, paxillin and PTEN. While oral administration of UA or US597 increases survival rate of melanoma lung metastasis in C57BL/6 mice, US597 treatment extend the survival rate above that of UA. Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis. We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities. Thus, UA and US597 are potential drug candidates for preventing cancer metastasis. Molecular and cellular study data suggest that UA and US597 modulate expression of cell adhesion molecules within focal adhesion signaling pathway leading to cancer cell motility.

UP12, a novel ursolic acid derivative with potential for targeting multiple signaling pathways in hepatocellular carcinoma.

Targeting cancer cell glucose metabolism is a promising strategy for cancer therapy. In past approaches to cancer drug discovery, ursolic acid (UA) has been chemically modified to improve its antitumor activities and bioavailability. Here, a novel ursolic acid (UA) derivative UP12 was developed via computer-aided drug design to explore potent anti-cancer agents and to examine possible mechanisms. The structural docking analyses suggested that UP12 could bind to the active sites of glucokinase (GK), glucose transporter 1 (GLUT1) and ATPase, which are the main enzymes involved in cancer glucose metabolism. We further investigated the synergistic effect between UP12 and glycolysis inhibitor 2-deoxy-d-glucose (2-DG) in inhibiting glucose metabolism of cancer cells. The pharmacological results showed that the combination enhanced depletion of intracellular ATP and decrease in lactate production, and pushed more cancer cells arrested in the S and G2/M cycle phases. The combination selectively down-regulated the expression of Bcl-2 and HKII proteins, up-regulated the expression of Bax and p53, and collectively resulted in enhanced apoptosis related to caspase-3, -8, and -9 activities, in addition to inhibition on the cell mitochondrial membrane potential. The animal studies further demonstrated that the combination exhibited significant antitumor activity without obvious toxicity. In summary, UP12 can interfere cancer cell metabolism pathway and further enhance the therapeutic effects of 2-DG likely through synergistic suppression of cancer cell glucose metabolism, making UP12 a likely new candidate for anti-cancer drug development.

Synthesis, spectral characterization, and in vitro cellular activities of metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486).

Mifepristone (RU486) is marketed and used widely by women as an abortifacient, and experimentally for psychotic depression and anticancer treatments. After administration, metapristone is found to be the most predominant metabolite of mifepristone. We hypothesized that adhesion of circulating tumor cells (CTCs) to vascular endothelial bed is a crucial starting point in metastatic cascade, and that metapristone can serve as a cancer metastatic chemopreventive agent that can interrupt adhesion and invasion of CTCs to the intima of microvasculature. In the present study, we modified the synthesis procedure to produce grams of metapristone, fully characterized its spectral properties and in vitro cellular activities, including its cytostatic effects, cell cycle arrest, mitochondrial membrane potential, and apoptosis on human colorectal cancer HT-29 cells. Metapristone concentration dependently interrupted adhesion of HT-29 cells to endothelial cells. Metapristone may potentially be a useful agent to interrupt metastatic initiation.

Synergism of ursolic acid derivative US597 with 2-deoxy-D-glucose to preferentially induce tumor cell death by dual-targeting of apoptosis and glycolysis.

Ursolic acid (UA) is a naturally bioactive product that exhibits potential anticancer effects. The relatively safe and effective molecule intrigued us to explore a way to further improve its anti-cancer activity and tumor-targeting specificity. In the present study, a series of structural modifications of UA was achieved, which resulted in significant increase in growth inhibition on various cancer cell lines with minimal effects on normal cells. The leading molecule US597 (UA-4) caused depolarization of mitochondrial membrane potential, cell arrest in G0/G1 phase and apoptosis/necrosis in a dose-dependent manner. Structural docking suggested that the carbon chains of the modified UA derivatives compete strongly with glucose for binding to glucokinase, the key glycolysis enzyme presumably active in cancer cells. The combination of 2-deoxy-D-glucose (2-DG) and UA-4 induced cell cycle arrest in G2/M phase, promoted caspase-dependent cell death, reduced hexokinase activity, aggravated depletion of intracellular ATP, decreased lactate production and synergistically inhibited cancer cell growth in vitro (HepG2) and in vivo (H22). Collectively, our findings suggest that the structural modification enhances efficacy and selectivity of UA, and the combination of UA-4 with 2-DG produces synergistic inhibition on hepatoma cell proliferation by dual targeting of apoptosis and glycolysis.

[An experimental study(II) on the inhibition of prostatic hyperplasia by extract of seeds of Brassica alba].

OBJECTIVE: To study the active components and their functionary mechanism of the extract of Brassica alba seeds, which inhibits experimental mice prostatic hyperplasia. METHOD: Prostatic hyperplasia of castrated male mice induced by testosterone propionate, the penetrability of capillary vessel of mice skin induced by histamine and the endermic flesh bud of rat induced by filter paper were used as experimental models. Sinalbin and beta-sitosterol separated from seeds of Brassica alba were used to test the activities. RESULT: Sinalbin and beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase(P < 0.01 or P < 0.05), Sinalbin(16.0 mg.kg-1.d-1)could significantly inhibit the hyperplasia of endermic flesh bud in rat induced by filter paper(P < 0.05), beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly decrease the penetrability of capillary vessel of mice skin induced by histamine. CONCLUSION: Sinalbin and beta-sitosterol have anti-androgen and anti-inflammation activities.

[An experimental study(I) on the inhibition of prostatic hyperplasia with extract of seeds of Brassica alba].

OBJECTIVE: To study the effective fraction of the extract of seeds of Brassica alba, which inhibits experimental mice prostatic hyperplasia. METHOD: An experimental model of prostatic hyperplasia of castrated male mice induced by testosterone propionate was made. Fractions I, II and III were prepared by extracting the seeds of Brassica alba successively with ether, ethanol and water under reflux. Total extract was prepared by extracting the seeds of Brassica alba with 60% ethanol under reflux. The total extract and the three fractions were used to test the activities. RESULT: Total extract, fractions I and II could not only significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase, but also decrease wet weight of preputial glands, while fraction III is inactive. CONCLUSION: Extract from seeds of Brassica alba can significantly inhibit mice prostatic hyperplasia induced by exterior hormone, possessing an activity of anti-androgen. Fractions I and II show an equivalent activity of total extract, which indicate that these fractions contain active components of seeds of Brassica alba which can inhibit prostatic hyperplasia.