Anti-Proliferative Potential of Fluorinated Curcumin Analogues: Experimental and Computational Analysis and Review of the Literature.

BACKGROUND: Curcuminoids, flavoring, and coloring agents in food have potent antioxidant, anti-tumor activity, and anti-inflammatory effects. However, they are rapidly metabolized to lesser active metabolites. Therefore, various studies have been conducted to synthesize new and stable curcumin analogues with enhanced therapeutic activity. METHODS: Fluorinated curcumin compounds (2a-2f) were synthesized by Knoevenagel condensation between fluorobenzaldehydes (1a-1f) with curcumin. Fluorinated demethoxycurcumin (3a) was synthesized by condensation between demethoxycurcumin and 3,4-difluorobenzaldehyde (1f). The structures of these compounds were confirmed by FTIR, 1H-NMR, 13C-NMR, 19FNMR, and mass spectroscopy. Antiproliferative activities of these synthetic compounds were evaluated against breast cancer cells (4T1), melanoma cancer cells (B16F10), and normal cell lines (NIH 3T3) using MTT assay. The interaction of curcumin, 2f and 3a with several proteins (1HCL, 2ZOQ, 3D94, 5EW3, 4WA9, 1XKK, 6CCY) was investigated. The structural preservation of the epidermal growth factor receptor (EGFR) was investigated by molecular dynamics simulation. RESULTS: The spectroscopic data obtained confirmed the proposed structure of fluorinated analogues. The results showed that compounds 2f and 3a inhibited cancer cells proliferation significantly more than other compounds. Compounds 2f and 3a showed the highest affinity and lowest binding energy with EGFR. The binding energies were -7.8, -10, and - 9.8 kcal/mol for curcumin, 2f and 3a with EGFR, respectively. The molecular docking results demonstrated that compounds 2f and 3a were firmly bound in a complex with EGFR via the formation of a hydrogen bond. CONCLUSION: In summary, we found that fluorinated demethoxycurcumin and fluorinated curcumin induces cancer cell death and binds to EGFR with high affinity.

Chemical composition and antibacterial properties of Peganum harmala L.

OBJECTIVE: The present study was conducted to investigate antibacterial properties of fruit and flower of Peganum harmala. MATERIAL AND METHODS: Column chromatography, followed by preparative thin layer chromatography (TLC) was used for final purification. The structure of pure alkaloids was determined using spectroscopic methods (1H-NMR, 13C-NMR, UV and MS). Smoke and extract of total alkaloids were investigated for antimicrobial activity against five different microorganisms (standards and hospital isolates). The antibacterial activity was evaluated using disc diffusion assay and minimum inhibitory concentration (MIC) was determined by serial dilution methods. RESULTS: Chemical investigation of the chloroform extract of ripe fruit and flower of P. harmala led to identification of three alkaloids in ripe fruit and two alkaloids in the flower and leaves of this plant. Alkaloids identified in ripe fruit were harmine, peganine (vasicine) and harmaline. Two alkaloids, harmine and peganine, were detected in the flower of P. harmala, while harmaline was only found in the ripe fruit. The total alkaloids of flower were compared with total alkaloids of ripe fruit by TLC method. Fruits and flowers had 3.12 and 3.27% alkaloid contents, respectively. CONCLUSION: Our results showed that the alkaloids and smoke were specifically more effective on Candida albicans and Gram- positive bacteria (Micrococcus luteus and Staphylococcus aureus), while Gram- negative bacteria, especially Pseudomonas aeruginosa, were less sensitive.

Altered serum Zinc and Copper in Iranian Adults who were of normal weight but metabolically obese.

Metabolically obese normal weight (MONW) individuals are potentially at increased risk of developing metabolic syndrome. Serum zinc and copper concentrations were assessed in individuals with MONW to determine whether MONW is associated with altered serum zinc and/or copper status. Normal weight subjects (total n = 2419; 1298 men and 1121 women), were recruited as part of Mashhad Stroke and Heart Association Disorder (MASHAD) Study cohort. They were divided into two groups according to the presence or absence of MetS, defined using IDF criteria. Serum zinc and copper concentrations were determined by atomic absorption. Of the 2419 normal weight adults, 377 had MetS. Of this group, 53.7% and 49.7% had a serum zinc <70 µg/dl (Q1) (p = 0.001) or a serum copper <79 µg/dl (Q1) respectively. Furthermore, 27.3% had a serum copper >131 µg/dl (Q4) (p = 0.034), and 18.8% had a serum zinc >95 µg/dl (Q4). Logistic regression analysis was performed to determine the odds ratio (OR) for an association of serum zinc, copper and zinc to copper ratio with MetS in normal weight subjects. The subjects with a serum zinc >95 µg/dl (Q4) had 0.386 [OR: 0.614(95%CI 0.457-0.823)] lower chance of MetS (p = 0.001) and the subjects with a serum copper >131 (Q4) had OR 1.423 (95% CI: 1.09-1.857) higher chance of MetS (p = 0.009). These data remained significant after adjustment for age and sex, for serum zinc and copper, respectively. Furthermore, our results strongly suggested that zinc and copper were the independent risk factor for metabolic syndrome in normal weight subjects. There is an imbalance between serum copper and zinc concentrations among individuals with MONW when compared with normal BMI individuals without MetS. This may increase the risk of individuals with MONW developing conditions associated with this imbalance, such as diabetes and cardiovascular disease.

Does Biosynthetic Silver Nanoparticles Are More Stable With Lower Toxicity than Their Synthetic Counterparts?

Control of size and shape is a challenge in nanoparticle synthesis. Synthetic and biosynthetic (both extracellular and intracellular) methods are used to prepare silver nanoparticle (SNP). In this study, the behavior of three strains of Staphylococcus aureus (S. aureus) was investigated in the presence of silver nitrate intra- and extracellularly. S. aureus strains biosynthesized SNPs intracellularly, while in the method of the extracellular biosynthesis, none of the strains could produce the SNP under different conditions (dark, bright light, and the presence of nitrate ion). Intracellular SNPs were purified. The results of this study and previous results were used to compare different properties of the biosynthetic (intra- and extracellular) and synthetic SNPs in terms of shape, size, zeta potential, stability, and toxicity. The results confirmed lower toxicity of biosynthetic SNPs in-vitro assays, and their more stability with less aggregation compared to the synthetic ones. Also, the biosynthetic nanoparticles were found uniform and small. These nanoparticles may be useful for being employed as biosensors.

Association Between Trace Element Status and Depression in HTLV-1-Infected Patients: a Retrospective Cohort Study.

Depression and Anxiety are two important public health problems that are known to be associated with viral infections. The association between the intake of nutrients such as zinc and copper with symptoms of depression has been studied previously. The aim of the current study was to investigate the association between depression with human T cell lymphotropic virus type 1 (HTLV-1) infection and serum content of zinc and copper in a large Iranian population cohort. The study population consisted of 279 HTLV-1-positive patients who were identified after recruitment as part of a large cohort study: the Mashhad Stroke and Heart Association Disorder (MASHAD) study. They were divided into two groups of diagnosed with or without depression based on their symptoms. Serum zinc and copper levels of all subjects were measured using the flame atomic absorption spectrometry. The population sample comprised of 279 individuals infected with HTLV-1 of whom 192 (68.8%) were women. The mean serum zinc in the group with and without depression was 78.69 ± 13.79 µg/dl and 86.87 ± 19.44 µg/dl, respectively (p < 0.001). Also, the serum copper level was higher in the depressive group (116.75 ± 39.56) than in the non-depressive group (104.76 ± 30.77) (p 0.004). The association between serum zinc and copper with depression in HTLV-1-infected patients which was shown in this study could be considered in the treatment strategies in these patients.

Association Between Hypertension in Healthy Participants and Zinc and Copper Status: a Population-Based Study.

The prevalence of hypertension (HTN) is increasing globally. It has been shown that there is an association between micronutrient deficiency and HTN. In the current study, we aimed to assess the association between HTN with serum copper and zinc concentrations in a large representative Iranian population. The participants were enrolled into the Mashhad stroke and heart atherosclerotic disorders study (MASHAD study), a cohort study that was initiated in 2010. Anthropometric indices were assessed using standard procedures. Systolic (SBP) and diastolic (DBP) blood pressures were measured using a standard mercury sphygmomanometer. Fasting blood glucose (FBG), lipid profile, uric acid and blood urea nitrogen (BUN), and hs-CRP were measured using routine methods. HTN defined as persons who had SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg and/or medication use. Flame atomic absorption (Varian AA240FS) was used to measure serum Zn and Cu concentrations. SPSS software was used for all statistical analyses. A total of 9588 participants were recruited into the MASHAD study project. Participants were divided into two groups; 5695 healthy (non-hypertensive) (mean age 45.85 ± 7.5 years) and 3893 hypertensive participants (mean age 51.18 ± 7.67 years). Systolic (p < 0.001) and diastolic blood pressure (p < 0.001) were significantly different for different serum copper quartiles. The participants with serum copper levels < 80 µg/dl had 1.33 times greater risk of an increased blood pressure than other participants. Participants with serum copper levels > 130 µg/dl had a 1.94-fold higher risk of raised blood pressure. Serum zinc was not associated with systolic blood pressure, but individuals in the first quartile level of serum zinc had a diastolic blood pressure that was significantly higher than other quartiles (p = 0.035). Serum copper is associated with blood pressure status in adults in a U-shaped relationship, with a range of serum copper between 80 and 130 µg/dl being associated with normal blood pressure.

Ethanol and Methanol Concentration in Commonly Used Brands of Ma-al-shaeer in Iran: Estimation of Dietary Intakes and Risk Assessment.

OBJECTIVES: Ma-al-shaeer is a popular beverage in Islamic countries. The aim of this study was to determine the concentrations of methanol and ethanol in most consumed brands of Ma-al-shaeer in Iran. METHODS: Eighty-one Ma-al-shaeer samples which commonly used in Iran were provided. Methanol and ethanol contents were determined by gas chromatography with flame ionization detector. RESULTS: The mean methanol concentrations in Iranian and foreign brands was 129.84±205.38 mg/L and 110.157±135.98 mg/L, respectively. Although mean ethanol contents of Iranian brands was 1.2±2.41 mg/L, ethanol level in foreign ones was lower than LOQ. CONCLUSION: Since the most Ma-al-shaeer brands had methanol pollution at different levels establishment of a definitive relationship between the methanol content and toxicological effects seem to be vital. EDI of methanol for Iranian people through consumption of Ma-al-shaeer was determined 0.023mg/kg bw/day.

Different behavior of Staphylococcus epidermidis in intracellular biosynthesis of silver and cadmium sulfide nanoparticles: more stability and lower toxicity of extracted nanoparticles.

Chemical reagents that are used for synthesis of nanoparticles are often toxic, while biological reagents are safer and cost-effective. Here, the behavior of Staphylococcus epidermidis (ATCC 12228) was evaluated for biosynthesis of silver nanoparticles (Ag-NPs) and cadmium sulfide nanoparticles (CdS-NPs) using TEM images intra- and extracellularly. The bacteria only biosynthesized the nanoparticles intracellularly and distributed Ag-NPs throughout the cytoplasm and on outside surface of cell walls, while CdS-NPs only formed in cytoplasm near the cell wall. A new method for purification of the nanoparticles was used. TEM images of pure CdS-NPs confirmed biosynthesis of agglomerated nanoparticles. Biosynthetic Ag-NPs were more stable against bright light and aggregation reaction than synthetic Ag-NPs (prepared chemically) also biosynthetic Ag-NPs displayed lower toxicity in in vitro assays. CdS-NPs indicated no toxicity in in vitro assays. Biosynthetic nanoparticles as product of the detoxification pathway may be safer and more stable for biosensors.

Characterization of Encapsulated Berberine in Yeast Cells of Saccharomyces cerevisiae.

Berberine was loaded in yeast cells of Saccharomyces cerevisiaeas a novel pharmaceutical carrier to improve the treatment ofmany diseases. The yeast-encapsulated active materialsshowedhigh stability and bioavailability due to the enhanced solubility and sustained releasing. In this study, different characteristics of prepared berberine loaded yeast cells (loading capacity, release kinetic order, MIC and stability) were evaluatedby different analytical methods (fluorescence spectroscopy, HPLC and SEM).The loading capacity was about 78% ± 0.6%.Berberine release patterns of microcapsules happened in two different stages and followed by zero and first-order kinetic,respectively. About 99% of all active material released during 34 h. MIC was improved by berberine loaded microcapsules in comparison withberberine powder. The microcapsules were completely stable. Berberine loaded Sac. Cerevisiae could be considered as a favorite sustained release drug delivery system. The yeast would be applied as an efficient carrier to improve various properties of different active materials.

New aspects of Saccharomyces cerevisiae as a novel carrier for berberine.

BACKGROUND: Berberine was encapsulated in yeast cells of Saccharomyces cerevisiae as novel carriers to be used in different food and drug industries. The microcapsules were characterized by differential scanning calorimetry (DSC), fourier transform infra red spectroscopy (FT-IR) and fluorescence microscopy. The encapsulation factors such as plasmolysis of yeast cells which affects the % encapsulation yield were studied. RESULTS: Fluorescence microscopy showed the yeast cells became fluorescent after encapsulation process. DSC diagram was representing of new peak for microcapsule which was not the same as berberine and the empty yeast cells peaks, separately. FTIR spectrums of microcapsules and yeast cells were almost the same. The plasmolysed and non plasmolysed microcapsules were loaded with berberine up to about 40.2 ± 0.2% w/w. CONCLUSION: Analytical methods proved that berberine was encapsulated in the yeast cells. Fluorescence microscopy and FTIR results showed the entrance of berberine inside the yeasts. DSC diagram indicated the appearance of new peak which is due to the synthesis of new product. Although plasmolysis caused changes in yeast cell structure and properties, it did not enhance berberine loading in the cells. The results confirmed that Saccharomyces cerevisiae could be an efficient and safe carrier for active materials.

Energy dispersive x-ray analysis of corrosion products in nondiscolored dentin and a dye-extraction study of Class 2 composite restorations following amalgam removal.

OBJECTIVE: To evaluate the effect of corrosion products on the microleakage of composite placed adjacent to nondiscolored dentin after amalgam removal. METHOD AND MATERIALS: Sixty Class 2 cavities were prepared on extracted premolars, which were divided into four equal groups according to the manner in which they were restored: group 1, light-cured packable composite (Elite LS) to establish a microleakage baseline; group 2, a high-copper amalgam (World Work) previously stored in 37°C normal saline for 6 months to create amalgam corrosion products; group 3, identical to group 2, but the amalgam was later replaced with composite, leaving the cavity walls intact; and group 4, identical to group 3 except the cavity walls were extended 0.5 mm after amalgam removal prior to insertion of the composite. Groups 1, 3, and 4 were kept in a 37°C normal saline for 1 week. Ten specimens from each of these three groups were randomly selected for dye-extraction testing, while dentin elemental microanalysis of five specimens from all four experimental groups was also conducted. Data were analyzed using ANOVA and the Tukey tests (α = .05). RESULTS: Corrosion products were not detected in group 4, and no statistically significant difference (P > .05) in microleakage was found between this group and group 1. The highest dye absorbance was associated with group 3 (P < .05). CONCLUSION: After amalgam removal, a 0.5-mm extension of the cavity walls could improve the dentinal marginal seal to replicate that of an initial composite restoration.

Determination of parathion, aldicarb, and thiobencarb in tap water and bottled mineral water in Mashhad, Iran.

Water is a necessity for life. Currently, because of different contaminations in tap water, most people prefer using bottled mineral waters. Pesticides (e.g., organophophorous, carbamates, etc.) are among the most dangerous chemicals that may be found in drinking waters, which can cause long- and short-term complications. Because all people consume at least 2 L of water per day, water-quality monitoring is vital. In this study, we determined the concentration of three pesticides (aldicarb, parathion, and thiobencarb) in 13 tap-water samples collected from 13 different urban areas and 10 samples of bottled mineral water in Mashhad, a major city in northeast Iran. Samples were analyzed by gas chromatography coupled with a pulsed flame photometric detector after solid-phase extraction. Results showed that 2 of 13 tap-water samples and 2 of 10 bottled mineral water trademarks were contaminated either by parathion or by thiobencarb or both, with concentrations ranging between 0.6 and 0.8 ppb. According to the defined guideline values, determined concentrations of pesticides are below the permissible World Health Organization level for these toxic agents, and it is considered that drinking these tap waters and bottled mineral waters are safe for human consumption.

Determination of heavy metals in different honey brands from Iranian markets.

A variety of elements are present in honey at different concentrations. Although some of these heavy metals and trace elements are useful nutrition, at higher levels they could cause health problems. In order to achieve confidence about food safety, regular monitoring of food quality is necessary. In this study, heavy metals and trace element contents were determined by inductively coupled plasma atomic emission spectrometer in 10 different honey brands from Iranian markets. All heavy metal contents in these samples were within ranges as reported in literature, except for Hg, Al and As. Compared with recommended daily intakes, it is concluded that heavy metals or trace elements intoxication following honey consumption in Iran is unlikely.

Nicotine content of domestic cigarettes, imported cigarettes and pipe tobacco in iran.

BACKGROUND: There are many different kinds of cigarettes and tobacco available in the market. Since nicotine content of various brands of cigarettes are very variable, therefore evaluation and comparison of nicotine content of different brands of cigarettes is important. The goal of the present study was to determine and compare nicotine content of various domestic and imported cigarettes available in the area. METHODS: Fourteen popular imported brands and nine popular domestic brands of cigarettes and three available brands of tobaccos were investigated for the amounts of nicotine content. Nicotine was extracted from each cigarette and tobacco samples and was analyzed by high performance liquid chromatography (HPLC) method. FINDINGS: The amount of nicotine in each cigarette was from 6.17 to 12.65 mg (1.23 ± 0.15 percent of tobacco weight in each cigarette) in domestic cigarettes. It was between 7.17-28.86 mg (1.80 ± 0.25 percent of tobacco weight in each cigarette) for imported cigarette, and between 30.08- 50.89 mg (3.82 ± 1.11 percent) for the pipe nicotine. There was significant difference in nicotine amount between imported and domestic brands of cigarettes. There was also no significant difference in nicotine content between light and normal cigarettes in imported brands. CONCLUSION: Nicotine content of all tested cigarettes, imported and domestic brands, were higher than the international standard.