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Background: Discovering new chemotherapy drugs and techniques with the least side effects is one of the most important and challenging issues in recent years worldwide. Chlorambucil is an anticancer drug that is still commonly used as a primary treatment in treating some cancers, but it can cause side effects., Objective: In this study, we decided to use chitosan as a carrier to enhance the uptake of chlorambucil and reduce the toxicity of this drug., Methods: After producing this nanoconjugate compound and analysing its structure by FTIR, DLS and AFM analysis, we investigated the therapeutic and biological effects of this nanoconjugate compound on the MCF-7 cell line (breast cancer)., Results: The results of the MTT assay showed that this nanoconjugate compound not only retained its anticancer effect against chlorambucil but also showed less abnormal toxicity. In addition, in vitro cellular uptake by flow cytometry indicated the better uptake final product into the MCF-7 cells. The detection of apoptosis induced cell death was confirmed by RT-PCR., Conclusion: This study has created a prospective pathway for targeting cancer cells using chitosan., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Breast cancer is the most common type of cancer in women worldwide. There have been many efforts for early breast cancer detection and among them molecular imaging have been extremely of high importance. Single-photon emission computed tomography (SPECT/CT) is a kind of imaging technique able to reveal crucial information with using radiopharmaceuticals. In this study, Technetium-99m-(DOTA-NHS-ester)-Methionine radiopharmaceutical was synthesized. Between 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono-N-hydroxysuccinimide ester (DOTA-HNS ester) (MACROCYCLICS, DOTA-NHS ester, Plano, Texas, USA) and methionine(marker) were conjugated. The DOTA-HNS ester-Methionine was labeled with Technetium-99m (Inter-Medical, Technetium-99m, Bergamo, Italy). The synthesized radiopharmaceutical was used in SPECT/CT imaging for breast cancer diagnosis. For radiopharmaceutical evaluation, MTT assay for cellular toxicity, biodistribution, cellular uptake and radiochemical purity were employed.Technetium-99m-(DOTA-NHS-ester)-Methionine radiochemical had less cellular toxicity in human embryonic kidney cells 293 cell line (HEK293). Cellular uptake was indicated higher percent with use of Methionine as a marker, and radiochemical purity was high. Based on the results Technetium-99m-(DOTA-NHS-ester)-Methionine radiochem may be a better option for early detection of breast cancer. Further study is recommended to confirm these findings in clinical practice., (Copyright © 2019. Published by Elsevier B.V.)

Background: Cancer is an important cause of human death worldwide. During the last decades, many anticancer agents with anti-tubulin mechanism have been synthesized or extracted from nature and some of them also entered clinical use. Indibulin is one of the most potent tubulin polymerization inhibitors with minimal peripheral neuropathy, which is a big problem by some of the antimitotic agents such as taxanes and vinka alkaloids. With respect to this giant benefit, herein we decided to design and synthesize novel indibulin related compounds and investigate their anticancer activity against HT-29, Caco-2 and T47-D cancerous cell lines as well as NIH-T3T as normal cell line., Objective: The aim of this study was to synthesize new anti-cancer agents and evaluates their cytotoxic activity on diverse cancerous and normal cell lines., Method: Target compounds were synthesized in multistep reaction and cytotoxic activity was investigated by MTT cell viability assay., Results: Herein, nine novel target compounds were synthesized in moderate to good yield. Some of the compounds exerted good cytotoxic activity against cancerous cell lines. Annexin V/PI staining showed that compound 4g could induce apoptosis and necrosis in HT-29 cell line., Conclusion: It is valuable to do further investigation on compound 4g which showed the highest activity against HT-29 and Caco-2 (IC50 values are 6.9 and 7 µM respectively). Also, synthesis of new derivatives of current synthesized compounds is suggested., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Brain tumor is a lethal, fast growing cancer and a difficult case for treatment. Receptor-mediated endocytosis has been recognized as one of the most effective methods for drug delivery to brain tissue by overcoming obstacles associated with conventional therapeutics. In this work, a targeted theranostic drug delivery system (DDS) was prepared based on gold‑iron oxide nanocomposites (Fe 3 O 4 @Au NCs). Lipoic acid-curcumin (LA-CUR) was synthesized and introduced as a novel anticancer drug, and glutathione (GSH) was exploited as the targeting ligand. Both LA-CUR and GSH were easily attached to Fe 3 O 4 @Au NCs via Au-S interaction. As a negatively charged nanocarrier, the prepared DDS showed relatively less protein adsorption. Accordingly, hemocompatibility assays (complement, platelet, and leucocyte activation) revealed its hemocompatible virtue, especially in respect of free LA-CUR. GSH functionalization led to 2-fold increase of cellular uptake in GSH receptor-positive astrocyte cells which could primarily indicate the probable ability of the DDS to bypass BBB. Cytotoxicity and apoptosis assays together showed the noticeably enhanced cytotoxicity of LA-CUR against cancerous U87MG cells (IC50=2.69μg/ml) in comparison with curcumin (IC50=21.31μg/ml); moreover, the DDS demonstrated relatively higher cytotoxicity against cancerous U87MG cells than normal astrocyte cells which was in accordance with pH sensitive mechanism of LA-CUR release. Besides, the results of in vitro magnetic resonance imaging (MRI) (relaxation rate (r 2 )=80.73 (s -1 ·mM -1 )) primarily revealed that the DDS can be applied as a negative MRI contrast agent. In sum, the prepared DDS appeared to be a promising candidate for brain cancer treatment and a favorable MRI contrast agent., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In spite of characterizing the role of protein kinase A (PKA) in activating biochemical mechanisms, few studies have investigated the effects of PKA inhibitors on memory functions. In the present study, we used Pavlovian fear conditioning paradigm to evaluate memory alterations caused by two doses of H89 (as a conditional inhibitor of PKA) alone and in combination with amyloid-β (Aβ) in rats. Moreover, we used the Western blotting method to investigate the alterations in markers of transcription, oxidative stress, inflammation, and apoptosis pathways involved in memory impairment. Stereotaxic surgery was done to inject Aβ (30 ng/side) directly into the hippocampal CA1 area bilaterally and H89 (5 or 10 μM) intracerebroventricular unilaterally. One series of rats were trained 7 days after injections, then contextual and tone tests were conducted on days 8 and 9, respectively. Second series of rats were trained 14 days after the injections and tests were carried out on days 15 and 16. Our behavioral results showed that H89 (5 μM) not only has no destructive effect on memory, but also attenuates memory deficit caused by Aβ in combination groups. In contrast, H89 (10μM) has a reversible destructive effect on memory. Our molecular findings indicated that low dose of H89 increases CREB phosphorylation, Nrf2 and HO-1 which results in survival resistance to the stress. On the contrary, H89 with higher concentration leads to substantial increase of NF-κB and caspase-3 levels, which impair memory functions. In conclusion, our data suggest that H89 as a PKA inhibitor influences memory process through a dose and time dependent manner., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Tea is an agricultural product of the leaves, leaf buds, and internodes of various cultivars and sub-varieties of the Camellia sinensis plant, processed and vulcanized using various methods. Tea is a main beverage in Iranian food basket so should be free from toxic elements such as pesticides residue. There is no data bank on the residue of pesticides in the consumed black tea in Iran. The present study is the first attempt for monitoring of 25 pesticide residues from different chemical groups in tea samples obtained from local markets in Tehran, I.R. Iran during the period 2011. A reliable and accurate method based on spiked calibration curve and QuEChERS sample preparation was developed for determination of pesticide residues in tea by gas chromatography-mass spectrometry (GC/MS). The using of spiked calibration standards for constructing the calibration curve substantially reduced adverse matrix-related effects and negative recovery affected by GCB on pesticides. The recovery of pesticides at 3 concentration levels (n = 3) was in range of 81.4 - 99.4%. The method was proved to be repeatable with RSDr lower than 20%. The limits of quantification for all pesticides were ≤20 ng/g. 53 samples from 17 imported and manufactured brand were analyzed. Detectable pesticides residues were found in 28.3% (15 samples) of the samples. All of the positive samples were contaminated with unregulated pesticides (Endosulfan Sulfate or Bifenthrin) which are established by ISIRI. None of the samples had contamination higher than maximum residue limit set by EU and India.

Background: Plants of Labiatae are used in traditional medicine and phytotherapy. Rosmarinic acid (RA) is a phenolic compound which is found in many genus of Labiatae and exhibits important biological activities., Materials and Methods: In this investigation, RA contents of 29 species of Labiatae named Salvia officinalis, Salvia limbata, Salvia virgata, Salvia hypoleuca, Salvia macrosiphon, Salvia choloroleuca, Melissa officinalis, Origanum vulgare, Lavandula angustifolia, Rosmarinus officinalis, Thymus daenensis, Thymus citriodorous, Thymus pubescens, Thymus vulgaris, Zataria multiflora, Mentha piperita, Mentha pulegium, Mentha longifolia, Mentha spicata, Mentha aquatica, Mentha crispa, Perovskia artemisoides, Zhumeria majdae, Satureja hortensis, Satureja khuzistanica, Satureja bachtiarica, Satureja atropatana, Satureja mutica and Satureja macrantha were determined by using high-performance liquid chromatographic method., Results: The results showed that RA content in different species of Labiatae was 0.0-58.5 mg g(-1) of dried plants. The highest amount of RA was found in Mentha species especially M. spicata., Conclusion: M. spicata can be considered as a new source of rosmarinic acid .

Zearalenone (Zen) is a mycotoxin with estrogenic effect which contaminates cereals. In cell culture, Zen and its metabolite, alpha-Zearalenol (alpha-Zel), stimulate breast cancer cells growth. Today hormone-dependent cancers are important because of high incidence and death rate. Previous studies showed that Zen and alpha-Zel have an effect on hormone-dependent cancers. This study explains the effects of the mentioned compounds in comparison with Raloxifene as an anti-estrogen. Cell culture technique was used with MDA-MB-231 and T47D cells for evaluation of compounds. MDA-MB-231 cells were used as negative control and also for proving that treatment compounds merely affect, due to their proliferation activity in the applied doses. According to the Resazurine-based method, for toxicity assay, none of the test compounds have an effect on MDA-MB-231 cells but do effect the growth of T47D cells. Zen and alpha-Zel at low concentrations (10-8-10-9 M) stimulated T47D cell growth and Raloxifene strongly inhibited cell growth induced by Zen and alpha-Zel. There is a noticeable result in controlling diet of hormonal carcinogenic compounds and applying novel anti-estrogens for prevention and treatment of hormone-dependent cancers.

An HPLC method for determination of rofecoxib in human serum is presented. The method is based on pre-column derivatization of analyte to a phenanthrene derivative of the drug. Rofecoxib and the internal standard were extracted from serum using liquid-liquid extraction. Upon exposure to UV light, the drug was found to undergo a photocyclization reaction, giving a species with high absorbance. Validation of the method has been studied in the concentration range 10-500 ng ml(-1).

S-Adenosyl-L-methionine (SAM) is a methyl-donor compound which is actively involved in a variety of biochemical reactions. An assay has been developed permitting the quantitative measurement of SAM and its related metabolites (S-adenosylhomocysteine, decarboxylated SAM, methylthioadenosine, adenosine and adenine) in liver and cell cultures. As gradient reversed-phase chromatographic or cation-exchange chromatographic methods often resulted in overlapping peaks, a two-dimensional high-performance liquid chromatographic (HPLC) procedure was developed involving gradient reversed-phase chromatographic separation followed by ion-exchange chromatography. After precipitating large molecules in the sample by perchloric acid, gel permeation was carried out on a Sephadex G 25 column to separate small water-soluble metabolites from proteins and membrane fragments. The freeze-dried sample was injected onto an ODS column and a 0-10% acetonitrile gradient in 10 mM ammonium formate buffer (pH 2.9) (20 min, linear) was applied. The relevant fractions were collected and injected onto a cation-exchange column (Partisil SCX, 10 microns, 250 mm x 4.6 mm I.D.). Elution and quantification were carried out using ammonium formate buffers of various concentration (15-400 mM), pH 2.9. The detector response (254 nm) as a function of concentration was linear over the concentration range 30-500 pmol. The detection limits of the compounds after the two-dimensional chromatographic procedure ranged from 10 to 60 pmol and the recovery was higher than 70%. The reproducibility of the results obtained from given samples was within 9-22% for rat liver and 6-24% for mast cells.

S-Adenosyl-L-methionine (SAM) and its metabolites S-adenosyl-L-homocysteine (SAH) and methyl-thioadenosine (MTA) are endogenous compounds that are heavily involved in a variety of biochemical processes, and have therefore been the target for several assays in body fluids and tissues. Reversed-phase chromatographic behaviour of SAM and its metabolites has been studied by using Supelcosil LC-ABZ column, specially designed for analysis of acidic, basic, zwitterionic and neutral compounds, and on a Hypersil ODS column as a function of mobile phase pH. The retentions of the compounds, expressed by the capacity ratio (k'), are measured on both column with mobile phases comprised of 10% acetonitrile and 10 mM ammonium formate buffer with pH values ranging from 2 to 9. Higher selectivity is observed on Supelcosil LC-ABZ within pH range 4-6. Different retention properties are observed at very low pH and seemed as if the Supelcosil LC-ABZ column reduced the effect of the mobile phase pH by about 1 pH unit. Whilst the Supelcosil column can be recommended for the routine analysis of SAM and its related metabolites in biological fluids by using mobile phase pH 5, the Hypersil ODS column may be suggested for use with mobile phase pH values of 3-4.