Green Synthesis of Magnetic Nanoparticles Using Satureja hortensis Essential Oil toward Superior Antibacterial/Fungal and Anticancer Performance.

The biological synthesis of nanoparticles, due to their environmental and biomedical properties, has been of particular interest to scientists and physicians. Here, iron nanoparticles (FeNPs) were synthesized using Satureja hortensis essential oil. Then, the chemical, functional, and morphological properties of these nanoparticles were characterized by typical experiments such as Uv-Vis, FTIR, XRD, FE-SEM, PSA, zeta potential, EDX, and EDX mapping. The results indicated Fe nanoparticles' formation with a cubic morphological structure and a particle size in the range of 9.3-27 nm. The antimicrobial effects of these nanoparticles were further evaluated using disc diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungal concentration (MFC) against two gram-positive bacterial strains (Staphylococcus aureus and Corynebacterium glutamicum), two gram-negative bacterial strains (Pseudomonas aeruginosa and Escherichia coli), and one fungus species Candida albicans. The results showed that green-synthesized Fe nanoparticles possessed higher antimicrobial properties than Satureja hortensis essential oil against selected pathogenic microorganisms, especially Gram-negative bacteria. Finally, the anticancer effect of these Fe nanoparticles was investigated on human cancer cells, K-562, and MCF-7, by the MTT assay. The results showed the anticancer effect of these nanoparticles against selected cell lines.

High-level Expression and One-step Purification of Chimeric Antigen Containing HTLV-I-II Diagnostic Epitopes in Escherichia coli.

Purification and preparation of three diagnostic antigens used for the detection of human T-lymphotropic virus (HTLV)-I/-II infection in E.coli are different parts of a multi-step method. In this study, our aim was to design a chimeric protein for the simultaneous detection of HTLV-I and HTLV-II antibodies. Immunodominant B cell linear epitopes of envelope and capsid proteins of HTLV-I/-II were selected and linked together; using a suitable amino acid linker and a chimeric antigen (CA). The codon-optimized synthetic DNA encoding the CA was subcloned into the pGS21aexpression vector and CA expressed as His-GST fused protein in E. coli BL21 (DE3) cells. Then the recombinant CA was purified, using the Ni-NTA (Nickle Nitrilotriacetic acid) affinity chromatography under native conditions. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric scanning results showed that CA accounted for 15% of the total cellular proteins and approximately 50% of the expressed histidine-glutathione s-transferase-chimeric antigen (His-GST-CA) proteins were soluble. The CA was successfully purified in one step with a purity of greater than 90%, which is suitable for antigenicity evaluations. Enzyme-linked immunosorbent assay (ELISA) results showed that the GST fused CA reacted in a concentration-dependent manner with HTLV-I/-II infected sera and was able to distinguish normal serum from HTLV-I/-II infected one with a proper sensitivity. With further validation, CA, as described in the present study could be introduced as a novel reliable, cost-effective and easy alternative for the three separate HTLV-I/-II diagnostic peptide antigens, which is prepared as a fusion with GST.

Association between serum cell adhesion molecules with hs-CRP, uric acid and VEGF genetic polymorphisms in subjects with metabolic syndrome.

Metabolic syndrome (MetS) is associated with a pro-inflammatory state and endothelial dysfunction that places subjects with MetS at a higher risk of atherosclerosis. Inflammatory biomarkers are raised in patients at risk of developing cardiovascular diseases. In the current study, we aimed to examine the possible association between MetS and serum soluble adhesion molecules, hs-CRP, uric acid, and the genetic variations related to vascular endothelial growth factor (VEGF) gene. In this cross-sectional study, participants were enrolled from the Mashhad stroke and heart atherosclerotic disorders (MASHAD) study. The International Diabetes Federation criteria were used to define the MetS. Cell adhesion molecules (CAM) and serum hs-CRP were measured by ELISA and PEG-enhanced immunoturbidimetry method, respectively. We used a logistic regression analysis to determine independent associations of CAMs with the VEGF polymorphisms and MetS. Two hundred and 59 participants with and without MetS were enrolled. Participants with MetS and DM had a significantly higher serum E-selectin level (p < 0.05). Participants with a high serum E-selectin level had higher levels of hs-CRP, FBG, TG, uric acid, BMI and lower levels of serum HDL-C (p < 0.05). Interestingly, individuals with MetS with a genetic variant of the VEGF gene (rs6921438) had higher level of serum ICAM-1 (p = 0.04). There were significant associations between serum E-selectin concentrations and the presence of MetS, and its risk factors. Moreover, we demonstrated that MetS subjects with the rs6921438 genetic variant had a higher serum level of ICAM-1 (p < 0.05).

ErbB4 receptor polymorphism 2368A>C and risk of breast cancer.

PURPOSE: A number of single nucleotide polymorphisms (SNPs) in EebB4 gene have been studied, which has clarified their impact on breast cancer in different populations. Nevertheless, the importance of rs13423759 in breast cancer has not been studied and its effect remained almost unclear. In this paper, we evaluated the frequency of rs13423759 different alleles in Iranian population and statistically analyzed their association with breast cancer risk. MATERIALS AND METHODS: Allele-specific Primer PCR (ASP-PCR) was recruited in this study to genotype rs13423759 position in 172 breast cancer and 148 healthy control subjects. The genotypes of control and cases were analyzed statistically to find the association between rs13423759 alleles and breast cancer incidence and its clinicopathological characteristics. In silico studies were performed in order to find the mechanistic viewpoint of rs13423759 alleles in breast cancer. RESULTS: rs13423759 allele C was shown to be significantly associated with breast cancer risk, HER2 positivity and increased risk of metastasis. Reciprocally, allele A was correlated with the lowered risk of breast cancer. The in silico studies showed that rs13423759 allele C is capable to strengthen the interaction between miR-548as, an oncomiRNA, and ErbB4 mRNA, leading to its lowered concentration in the cells. CONCLUSION: rs13423759 allele C is significantly associated with the enhanced risk of breast cancer, elevated metastasis and HER2 positivity.

The effect of CYP2C9*2, CYP2C9*3, and VKORC1-1639 G>A polymorphism in patients under warfarin therapy in city of Kermanshah.

Polymorphism in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence warfarin dose requirement since patients with CYP2C9*2, CYP2C9*3 and VKORC1 mutant alleles require lower warfarin maintenance doses. Studies have reported the ethnic variations in the frequency of these genes within the various populations in Iran and other parts of the world. However, no such study has been done yet on Kurdish population in Kermanshah. From Kurdish population of Kermanshah province in Iran, a total of 110 patients who had heart surgery and taking warfarin, were genotyped for polymorphisms of VKORC1-1639 G>A, CYP2C9*2, and CYP2C9*3. Polymorphism genotyping was performed by sequencing as well as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using restriction enzymes of MspI, AVAII and KpnI, respectively. The frequencies of VKORC1-1639 GG, GA, and AA genotypes were 42%, 36%, and 22%, respectively and for CYP2C9 1*/1*, 1*/2*, 2*/2*, 1*/3*, 3*/3*, 2*/3* were 71%, 17%, 5.4%, 1.8%, 4.5%, and 0%, respectively. The frequency of VKORC1-1639A allele was 42.3% and the frequencies of CYP2C9*2 and *3 alleles were 14% and 5.4%, respectively. It was indicated that low warfarin dose requirements are strongly associated with the presence of CYP2C9 and VKORC1-1639 variant alleles. Our results confirmed the supply to understand the distribution of genomic biomarkers related to the drugs metabolism for future planning health programs.

Association of rs6921438 A

BACKGROUND: Genome-wide association studies (GWAS) have identified common variants at the Vascular-Endothelial-Growth-Factor (VEGF) gene locus, which appear to be associated with plasma VEGF concentrations. These factors are among the major risk factors for cardiovascular disease and metabolic syndrome (MetS). We have investigated the association between serum VEGF concentrations and a VEGF genetic variant (rs6921438 A

Concentration of lead and mercury in collected vegetables and herbs from Markazi province, Iran: a non-carcinogenic risk assessment.

The current study was undertaken to determine the concentration of Hg and Pb in ten types of collected green leafy vegetables and herbs from different agricultural sites of Markazi province, Iran as well as the gathered water and soil around them using inductively coupled plasma-optical emission spectroscopy (ICP-OES). Also, the potential health risk assessment by using target hazard quotient (THQ) and hazard index (HI) parameters was estimated. Based on the accumulation order, Artemisia dracunculus L with 56.147 ±â€¯17.30 µg/kg and Spinacia oleracea L with 1733.62 ±â€¯2264.7 µg/kg can uptake and accumulate more concentration of Pb and Hg in their tissues, respectively. Regarding gathered soil around vegetables, the concentration of Hg and Pb were measured as 52.056 ±â€¯16.25 µg/kg and 4993.83 ±â€¯1287.8 µg/kg, respectively. The transfer factor (TF) demonstrated that vegetables and herbs could absorb a high amount of Hg from the soil while these plants uptake less concentration of Pb thought their green leaves. The non-carcinogenic risk assessment showed the minimum, and maximum THQ was related to 15-24 and 35-44 age groups in the urban and rural consumers. Also, HI in the urban and rural areas was calculated as 8.492 and 9.012, respectively. Since HI > 1, exposure of the urban and rural areas of Markazi province to non-carcinogenic risk by consuming the green leafy vegetables and herbs is a source of concern.

The Effects of Flaxseed Oil Omega-3 Fatty Acids Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome (PCOS). METHODS: This randomized double-blind, placebo-controlled trial was conducted on 60 women with PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly assigned into two groups to receive either 1,000 mg flaxseed oil omega-3 fatty acids (n=30) or placebo (n=30) twice a day for 12 weeks. Metabolic, endocrine, inflammatory factors were quantified at baseline and after the 12-week intervention. RESULTS: After the 12-week intervention, compared to the placebo, flaxseed oil omega-3 supplementation significantly decreased insulin values (-2.6±7.7 vs.+1.3±3.9 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (-0.7±1.7 vs.+0.3±0.9, P=0.01), mF-G scores (-1.2±1.7 vs. -0.1±0.4, P=0.001), and increased quantitative insulin sensitivity check index (+0.01±0.02 vs. -0.01±0.02, P=0.01). In addition, supplementation with flaxseed oil omega-3 resulted in significant decreases in serum triglycerides (-5.1±20.9 vs.+9.7±26.1 mg/dL, P=0.01), VLDL-cholesterol (-1.0±4.2 vs.+1.9±5.2 mg/dL, P=0.01) and high-sensitivity C-reactive protein (hs-CRP) (-1.6±3.1 vs.+0.2±1.5 mg/L, P=0.004) compared to the placebo. We did not see any significant effect of flaxseed oil omega-3 supplementation on hormonal and other lipid profiles, and plasma nitric oxide levels. CONCLUSIONS: Overall, flaxseed oil omega-3 supplementation for 12 weeks in women with PCOS had beneficial effects on insulin metabolism, mF-G scores, serum triglycerides, VLDL-cholesterol and hs-CRP levels, but did not affect hormonal and other lipid profiles, and plasma nitric oxide levels.

The association between rs1972820 and the risk of breast cancer in Isfahan population.

CONTEXT: A number of single nucleotide polymorphisms (SNPs) in ERBB4 gene have been linked to increase the risk of breast cancer. However, no study has been dedicated to analyze the significance of microRNA-related SNP rs1972820, located in ERBB4 3'-untranslated region (UTR), in breast tumors. AIMS: Here, we investigated the frequency and association between rs1972820 and breast cancer. SUBJECTS AND METHODS: The rs1972820 genotypes in 182 samples were collected from 96 healthy people, and 86 breast cancer patients were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction. The frequency of genotypes was analyzed to find the association between rs1972820 and breast cancer risk. STATISTICAL ANALYSIS USED: Conditional logistic regression, odds ratios (ORs), the associated 95% confidence intervals (CIs), and Armitage's test were used in this study. RESULTS: In silico analysis suggested that rs1972820 located in the 3'UTR of ERBB4 gene affects the binding affinity of miR-3144-3p a potential oncomiRNA. Statistical analysis showed a significant association between SNP rs1972820 G allele and reduced breast cancer risk, odds ratio = 0.443 (95% CI: 0.196-0.998). CONCLUSIONS: rs1972820 SNP allele is significantly associated with the reduced risk of breast cancer and could be considered as a potential marker for breast cancer predisposition in population of Isfahan.

A Novel Mutation in SLC7A9 Gene in Cystinuria.

INTRODUCTION: Cystinuria is an inherited disorder affecting luminal transport of cystine and dibasic amino acids. Because of the poor solubility of cystine in urine, stone formation in the kidney occurs frequently. Cystinuria is associated with mutations in the SLC3A1 and SLC7A9 genes. Despite the population-specific distribution of mutations in the SLC7A9 genes, there are few genetic data reported for cystinuric patients from the Middle East. MATERIALS AND METHODS: Exon 4 of the SLC7A9 gene was sequenced in 21 patients with cystinuria, using the polymerase chain reaction and sequencing methods. RESULTS: A new variation in exon 4 of the SLC7A9 gene was identified, which was insertion of 1 adenine nucleotide between 2 cytosine nucleotides in position c.213-214insA. CONCLUSIONS: It seems to be important since it causes frame shift and it may be an important cause to make disease.

Aqueous extract of Launaea acanthodes induces glutamate uptake and GABA release in astrocyte cell culture via a ROS scavenging mediated process.

Launaea acanthodes is extensively used in the semiarid region of Iran for treatment of seizure. However, the underlying mechanism has not been studied well. In our previous study we showed that Launaea acanthodes extract could effectively stimulate GABA release from PC12 cell culture. The critical role of astrocytes in epileptic brain in regulation of neurotransmitter balance in central nervous system encouraged us to investigate the effect of Launaea acanthodes extract on GABA and glutamate release from astrocytes. Our results indicated that LA extract could stimulates both glutamate uptake and GABA release by astrocytes. The results confirmed this fact that GABA release by astrocytes in response to LA treatment is a glutamate uptake-dependent process. We showed that stimulation of GABA release by Launaea acanthodes is a gene expression based process which depends on glutamate uptake. We propose that glutamate uptake via glutamate transporter 3 could activate expression of glutamate decarboxylase which in turn transforms uptaken glutamate into GABA.

ESR1 single nucleotide polymorphism rs1062577 (c.*3804T>A) alters the susceptibility of breast cancer risk in Iranian population.

OBJECTIVES: Albeit single nucleotide polymorphisms related to ESR1 gene have been studied, only a number of them have been reported to be associated with breast cancer risk. rs1062577 is one of the most recent microRNA-related ESR1 SNPs; however, no study has been conducted to investigate the significance this polymorphism in Iranian population. In this study, we aimed to investigate the frequency and also the association between rs1062577 and breast cancer. MATERIALS AND METHODS: rs1062577 position was genotyped by Tetra-primer ARMS-PCR in totally 182 blood specimens obtained from breast cancer patients (n=86), and healthy blood donors (n=96). The distribution of different genotypes was statistically analyzed in terms of the potential association between rs1062577 different alleles, breast cancer risk and clinicopathological criteria of breast cancer patients. RESULTS: The statistical analyses confidently indicated that rs1062577 A allele is associated with the increased breast cancer risk in both univariate and multivariate regression models (Odds Ratio=8.403 and 32.602 respectively). rs1062577 T allele was statistically associated with stage I of breast cancer patients (p-value=0.025). In silico studies implied that rs1062577 A allele can alter the binding capacity of ESR1 mRNA and miRNAs via either breakage or formation of hydrogen bonds. CONCLUSION: rs1062577 A allele is significantly and dramatically associated with the elevated risk and greater stages of breast cancer.

Association of a Vascular Endothelial Growth Factor genetic variant with Serum VEGF level in subjects with Metabolic Syndrome.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of metabolic disorders that is associated with an increased risk of developing cardiovascular-disease, diabetes, and related diseases. Against this background, Vascular Endothelial Growth Factor (VEGF) plays an essential role in angiogenesis, vascular permeability, and hematopoiesis and its increased level is reported to be associated with increasing the risk of developing cardiovascular-disease, stroke and diabetes. Therefore the aim of present study was to explore the association of serum VEGF level and its associated genetic-polymorphism, rs10738760 (A>G) at 9p24.2, in 850 subjects with/without MetS. METHODS: MetS was defined according to the International-Diabetes-Federation criteria. Genotyping was carried out using Polymerase chain reaction-amplification refractory mutation system. Anthropometric/biochemical parameters, including FBG, Triglyceride, HDL, TC, etc., were determined followed by univariate and multivariate analyses. RESULTS: MetS patients had significantly higher levels of BMI, waist-circumference, cholesterol, triglyceride, Hs-CRP and SBP/DBP, while the HDL-C levels was lower in patients group, compared to control group (P<0.05). Moreover, our analysis showed that MetS patients with GA or AA genotypes had a significantly (P=0.03) higher serum level of VEGF. CONCLUSIONS: we demonstrate an association between a VEGF genetic variant with MetS, suggesting its role as a risk stratification factor for MetS.

rs11895168 C allele and the increased risk of breast cancer in Isfahan population.

OBJECTIVES: Some of the single nucleotide polymorphisms in EebB4 gene have been studied to date in order for finding their relevance to the risk of breast cancer. However, no study has been conducted to investigate the importance of rs11895168, a microRNA-related SNP located in ErbB4 3'UTR, in breast tumors. In this paper, we investigated the frequency and association between rs11895168 and breast cancer. MATERIALS AND METHODS: The rs11895168 was genotyped in 364 samples collected from 172 breast cancer patients and 192 healthy participants, using Tetra-primer ARMS PCR. The frequency of genotypes was analyzed to find the association between rs11895168 and breast cancer risk and also clinicopathological characteristics of patients. RESULTS: our in silico studies suggested that different alleles at rs11895168 affect the binding strength of miR-1276, a potential tumor suppressor. Statistical analysis showed a significant association between rs11895168 C allele-harboring genotypes and increased breast cancer risk. CONCLUSION: rs11895168 C allele is strongly and significantly associated with the increased risk of breast cancer and positivity of ER/PR tumor cells.

Folate decorated magnetite nanoparticles: synthesis and targeted therapy against ovarian cancer.

Doxorubicin (DOX) loaded folate-coated magnetic Fe3 O4 nanoparticles (MNPs) were prepared by co-precipitation and emulsification cross-linking method and uniform NPs with an average particle size of 15 (bare) and 35 nm (FA-MNPs), with high encapsulation efficiencies (EE), were obtained. The release profiles of conjugated DOX showed that pH 6.0 provided suitable conditions for proper drug release. IC50 analysis of C30 and CP70 cell lines after 96 h (4 days) exposure to DOX-FA-MNPs showed that the most significant IC50 were at 5.4 ± 0.6 and 11.2 ± 2.7 mM DOX loaded onto the FA-MNPs. Thus CP70 cells are more resistant to lower concentrations of drug compared to C30 cells (P < 0.05). C30 and CP70 cells reached 91 and 81.8% apoptosis after administration of DOX-FA-MNPs (5 mg/mL) compared to 49.2 and 46.6% after administration of the free drug, respectively (P < 0.05). this study indicates that FA modified MNPs enhances the DOX-induced apoptosis in both of the human ovarian cancer cell lines with sharp decreases in the levels of bcl-2 and surviving, and increased expression of caspase-3.

Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia-reperfusion in rat model.

BACKGROUND: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats. METHODS: Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process. RESULTS: The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group (P < 0.05). EPO administration decreased levels of BUN and Cr significantly (P < 0.05), and KTDS and KW insignificantly (P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite (P < 0.05). CONCLUSIONS: EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.

Hepatotoxicity of Dorema aucheri (Bilhar) in albino mice.

BACKGROUND: The geographic map of cancer prevalence differs due to environmental and dietary factors in various populations. High prevalence of a number of cancers in some regions is thought to be attributed to local dietary habits. Dorema aucheri (Bilhar) is used commonly as an herbal medicine in some regions including Iran. The aim of this study was to evaluate whether Dorema aucheri has carcinogenic effects in albino mice or not. METHODS: The Dorema aucheri leaves were extracted by Soxhlet method and were injected intraperitoneally and randomly into 28 healthy albino mice which were divided into seven groups. One was put aside as the non-injected control group. The second control group was chosen to be injected by a known carcinogen. Another group was injected by carcinogen and then, Bilhar extract. The left four groups were injected the extracts in a dose- dependent manner, increasingly in the range of 0.4 - 3.2mL/kg. Extract injections were repeated every 48- hour intervals for three times. Then, liver and serum samples were analyzed biochemically and pathologically. RESULTS: The pathologic and biochemical studies showed that the injection of plant extracts caused necrosis, inflammation of the liver tissue, cell proliferation, cholestasis, and there were significant increases in release of liver enzymes [ALP, ALT (SGPT) and AST (SGOT)] and bilirubin compared to the non-injected control group. The level of liver damage was dose dependent. CONCLUSIONS: Dorema aucheri has potential hepatotoxic capacities and possibly this may be related to the high prevalence of cancer in some regions of Iran.

Effect of Consuming Zinc-fortified Bread on Serum Zinc and Iron Status of Zinc-deficient Women: A Double Blind, Randomized Clinical Trial.

After iron deficiency, zinc deficiency is the major micronutrient deficiency in developing countries, and staple food fortification is an effective strategy to prevent and improve it among at-risk-populations. No action has been taken to reduce zinc deficiency via flour fortification so far in Iran, and little is known about the influence of zinc fortification of flour on serum zinc and the iron status, and also about the optimum and effective amount of zinc compound that is used in food fortification. The objective of this study is to evaluate the influence of consuming zinc-fortified breads on the zinc and iron status in the blood serum. In this study, three types of bread were prepared from non-fortified and fortified flours, with 50 and 100 ppm elemental zinc in the form of sulfate. Eighty zinc-deficient women aged 19 to 49 years were randomly assigned to three groups; The volunteers received, daily, (1) a non-fortified bread, (2) a high-zinc bread, and (3) a low-zinc bread for one month. Serum zinc and iron were measured by Atomic Absorption before and after the study. Results showed a significant increase in serum zinc and iron levels in all groups (p < 0.001) except in the control (p > 0.05). Absorption of zinc and iron in the group that consumed high-zinc bread was significantly greater than that in the group that received low-zinc bread (p < 0.01). It was concluded that fortification of flour with 50-100 ppm zinc was an effective way to achieve adequate zinc intake and absorption in zinc-deficient people. It also appeared that consuming zinc-fortified bread improved iron absorption.