Therapeutic potential of natural products in glioblastoma treatment: targeting key glioblastoma signaling pathways and epigenetic alterations.

Glioma is the most common primary tumor of the nervous system, and approximately 50% of patients exhibit the most aggressive form of the cancer, glioblastoma. Currently, considerable research in glioblastoma therapeutics is aimed at developing vaccines or drugs to target key molecules for combating this disease. Studies on plant natural products from spices, vegetables, fruits, teas, and traditional medicinal herbs display that these plant-derived natural products can act as effective antioxidant and anti-tumor agents. The advancements in metabolomics and in genomics have enabled researchers to better evaluate the potential use of immunomodulatory natural plant products for treatment of different cancerous diseases. The glioblastoma protective activities of the different natural plant products lie in their effects on cellular defenses such as antioxidant enzyme systems, detoxification and the stimulation of anti-inflammatory, anti-metastasis responses and by modifying epigenetic alterations, often through targeting specific key transcription factors such as activator protein, nuclear factor kappa B, signal transducers and activators of transcription and so on. Here, we review recent knowledge on the molecular mechanisms by which different inflammatory activities are linked to progression of glioblastoma and the particular immunomodulatory plant products that may reduce inflammation and the associated progression and metastasis of glioblastoma both in vitro and in vivo. Furthermore, their impact on the epigenetic alterations will also be discussed.

Molecular cloning, expression, and characterization of E2F transcription factor 4 from Antheraea pernyi.

The E2F transcription factor family is distributed widely in eukaryotes and has been well studied among mammals. In the present study, the E2F transcription factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino acid sequence of 264 amino acid residues. The recombinant protein was expressed in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The deduced amino acid sequence displayed significant homology to an E2F4-like protein from Bombyx mori L. Quantitative real-time polymerase chain reaction analysis revealed that E2F4 expression was highest in the integument, followed by the fat body, silk glands, and haemocytes. The expression of E2F4 was upregulated in larvae challenged by bacterial (Escherichia coli, Micrococcus luteus), viral (nuclear polyhedrosis virus), and fungal (Beauveria bassiana) pathogens. These observations indicated that E2F4 is an inducible protein in the immune response of A. pernyi and probably in other insects.

Novel lipoate-selective membrane sensor for the flow injection determination of alpha-lipoic acid in pharmaceutical preparations and urine.

A potentiometric lipoate-selective sensor based on mercuric lipoate ion-pair as a membrane carrier is reported. The electrode was prepared by coating the membrane solution containing PVC, plasticizer, and carrier on the surface of graphite electrode. Influences of the membrane composition, pH, and possible interfering anions were investigated on the response properties of the electrode. The sensor exhibits significantly enhanced response toward lipoate ions over the concentration range 1 x 10(-7) molL(-1) to 1 x 10(-2) molL(-1) with a lower detection limit of (LDL) of 9 x 10(-8) molL(-1) and a slope of -29.4 m V decade(-1), with S.D. of the slope is 0.214 mV. Fast and stable response, good reproducibility, long-term stability, applicability over a pH range of 8.0-9.5 is demonstrated. The sensor has a response time of

A novel membrane sensor for histamine H1-receptor antagonist "fexofenadine".

The construction and general performance of thirteen new polymeric membrane sensors for the determination of fexofenadine hydrochloride based on its ion exchange with reineckate, tetraphenylborate and tetraiodomercurate have been studied. The effects of membrane composition, type of plasticizer, pH value of sample solution and concentration of the analyte in the sensor internal solution have been thoroughly investigated. The novel sensor based on reineckate exchanger shows a stable, potentiometric response for fexofenadine in the concentration range of 1 x 10(-2) - 2.5 x 10(-6) M at 25 degrees C that is independent of pH in the range of 2.0 - 4.5. The sensor possesses a Nernstian cationic slope of 62.3+/-0.7 mV/concentration decade and a lower detection limit of 1.3 x 10(-6) M with a fast response time of 20 - 40 s. Selectivity coefficients for a number of interfering ions and excipients relative to fexofenadine were investigated. There is negligible interference from almost all studied cations, anions, and pharmaceutical excipients, however, citrizine that has a structure homologous to that of fexofenadine was found to interfere. The determination of fexofenadine in aqueous solution shows an average recovery of 99.83% with a mean relative standard deviation (RSD) of 0.5%. Direct potentiometric determination of fexofenadine in tablets gave results that compare favorably with those obtained by standard spectrophotometric methods. Potentiometric titration of fexofenadine with phosphomolybdic acid as a titrant has been monitored with the proposed sensor as an end point indicator electrode.

Gallamine-tetraphenylborate-modified carbon paste electrode for the potentiometric determination of gallamine triethiodide (flaxedil).

The construction and general performance of a novel modified carbon paste electrode for the determination of gallamine triethiodide have been developed. The electrode shows a stable, potentiometric response for gallamine in the concentration range 1 x 10(-3)-2 x 10(-6) M at 25 degrees C independent of pH in the range 5-8. The electrode passes a near-Nernstian cationic slope of 17.0+/-0.7 mV and lower detection limit of 1 x 10(-6) M with a fast response time of 20-45 s. Selectivity coefficients for gallamine relative to a number of interfering substances were investigated. There is a negligible interference from the studied cations, anions, and pharmaceutical excipients. The determination of gallamine in aqueous solution shows an average recovery of 99.5% and a mean relative standard deviation (RSD) of 1.4% at 100 microg/ml. The direct determination of gallamine in injection solution gave results that compare favorably with those obtained by the British pharmacopoeia method. Potentiometric titration of gallamine with sodium tetraphenylborate and phosphotungstic acid as a titrant has been monitored with the modified carbon paste electrode as an end-point indicator electrode.

PVC membrane ion selective electrode for the determination of pentachlorophenol in water, wood and soil using tetrazolium pentachlorophenolate.

A novel PVC membrane electrode selective for the determination of pentachlorophenolate (PCP) ion based on 2,3,5-triphenyl-2H-tetrazolium (TPT) pentachlorophenolate ion pair as an electroactive material is described. The electrode shows a linear response for PCP ion over the concentration range of 6x10(-5) to 1x10(-2) M with lower detection limit of 4x10(-5) M at 25 degrees C. The electrode posses a Nernstian slope of -55.0+/-1.0 mV/decade and a fast potential response of 45 s, which is almost constant over a pH range of 5.5-10.5. Selectivity coefficient data for some common ions show negligible interference, however, 2,4,6-trichlorophenolate and cetylpyridinium ions interfere. An average recovery of 96.2% with relative standard deviation of 2.3% has been achieved for the determination of 75.0 ppm PCP in wastewater samples. The determination of PCP in soil and wood samples gave results that compare favorably with those obtained by gas chromatography. The electrode has been utilized as an end point indicator electrode for the determination of PCP using potentiometric titration.

Cetylpyridinium-iodomercurate PVC membrane ion selective electrode for the determination of cetylpyridinium cation in Ezafluor mouth wash and as a detector for some potentiometric titrations.

A potentiometric method is described for the determination of cetylpyridinium (CP) cation using a polyvinyl chloride powder (PVC) membrane sensor based on CP-iodomercurate ion pair as an electroactive material. The sensor shows a linear response for CP ion over the concentration range of 2x10(-6)-1x10(-3) M at 25 degrees C. The electrode posses a sub-Nernstian slope of 29.0+/-0.4 mV decade(-1), which has been thoroughly discussed.The electrode shows a fast potential response of approximately 50 s, which is almost constant over a pH range of 3.0-6.0. Selectivity coefficient data for some common ions show negligible interference, however, cetyltrimethylammonium bromide (CTMAB) interferes significantly. An average recovery of 98.8% for CP with an average relative standard deviation (R.S.D.) of 1.2% has been achieved. The determination of CPC in Ezafluor mouth wash gave result that compare favorably with those obtained by the British Pharmacopoeia method. The CP electrode has been utilized as an end point indicator electrode in potentiometric titration of some anions, and applied for the determination of anionic surfactants in some commercial detergents and waste water.

Hydrogen chromate PVC matrix membrane sensor for potentiometric determination of chromium(III) and chromium(VI) ions.

A novel potentiometric Cr(6+) PVC matrix membrane sensor incorporating nickel tris(1,10-bathophenanthroline) hydrogen chromate as an electroactive material and 2-nitrophenyl phenyl ether as solvent mediator is described. In a phosphate buffer solution of pH 5, the sensor displays a rapid and linear response for Cr(6-) over the concentration range 2 x 10(-2)-8 x 10(-6) M with an anionic slope of 55.5 +/- 0.2 mV decade(-1) and a detection limit of the order of 0.4 microg ml(-1). The sensor is used for sequential determination of Cr(6+) and Cr(3+) by direct monitoring of Cr(6+) followed by oxidation of Cr(3+) and measurement of the total chromium. The average recoveries of Cr(3+) and Cr(6+) at concentration levels of 0.5-50 microg ml(-1) are 98.1 +/- 0.4% and 99.1 +/- 0.4% respectively. Redox and precipitation titrations involving Cr(6+) as a titrant are monitored with the sensor. Cr(3+) and/or Cr(6+) in wastewaters of some industries (e.g., leather tanning, electroplating, aluminum painting) and the chromium contents of some alloys and refractory bricks are assessed. The results agree fairly well with data obtained using the standard diphenylcarbazide spectrophotometric method.