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This study aimed to investigate the polymorphism of matrix metalloproteinase -3 (MMP-3) gene and its expression in the serum of infertile female patients received in vitro fertilization and embryo transfer (IVF-ET). To do so, 100 women with unsuccessful IVF-ET (IVF^–) and 100 women with successful IVF-ET procedure and clinical pregnancy (IVF⁺) were included. Genetic polymorphism and serum concentration of MMP3 were investigated by ARMS-PCR and ELISA, respectively. The results showed no significant association between MMP-3 gene polymorphism and IVF-ET outcome among the two groups studied. However, a significant decrease in the concentration of MMP-3 serum in the IVF^– group was observed in comparison with the IVF⁺ group (P=0.000002). Moreover, we showed that the serum MMP-3 levels in CC, AC and AA genotypes in the IVF^– group were 33, 65.33 and 86 ng/ml, respectively. In conclusion, while there is no significant difference between MMP-3 promoter polymorphism and IVF-ET outcome between the IVF⁺ and IVF^- groups, a significant decrease in MMP-3 serum levels in IVF^- group was seen as compared with the IVF⁺ group. It could be also suggested that the CC genotype is associated with a decreased level of MMP-3 serum concentration and may be associated with IVF-ET failure.
 

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Peroxidase catalyzes different oxidation of substrates using hydrogen peroxide, a reactive oxygen specie (ROS). ROS, at low concentrations, act as messenger to regulate intracellular signaling, whereas, at high concentrations, they can overcome the immune system by creating oxidative stress. Some common beverages such as coffee, tea and soft drinks contain high levels of xanthine alkaloids including theophylline and theobromine. In this study, the effect of theophylline and theobromine on peroxidase activity was kinetically studied by measuring the absorption of 4-aminoantipyrine, oxidized in the presence and absence of theophylline and theobromine at 510 nm for 3 minutes. The results showed that theobromine and theophylline acted as inhibitors with IC₅₀ of 0.50 and 0.55 mM, respectively. K_m and V_max values showed that both compounds are non-competitive inhibitors. The values of K_i were calculated as 0.03 and 0.045 mM for theobromine and theophylline, respectively. Lower values of K_i and IC₅₀ for theobromine compared to theophylline indicates that theobromine has a higher inhibition strength and binding tendency to the enzyme-substrate complex. Hence, it is concluded that theobromine has a stronger inhibitory effect on POD activity.
 
 

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Human serum albumin is one of the most important blood proteins that has the ability to bind a wide range of compounds and different drugs. Hence, knowing how drugs bind to albumin is crucial to understand their pharmacokinetics and pharmacodynamic properties. The binding of drugs to protein affects the drug's excretion, distribution and interaction in the target tissues. Nicotinamide (NA) is a safe and inexpensive medical supplement that used to prevent and treat vitamin B3 deficiency. In this research, the molecular mechanism of the interaction between nicotinamide and human serum albumin was studied by the utilization of spectroscopic and molecular docking methods. The effects of temperature, acidic/basic pHs, metal ions, urea, and glucose on the interaction between nicotinamide and human serum albumin were also investigated. The spectroscopic studies indicated that the interaction between nicotinamide and human serum albumin is mainly controled by hydrophobic forces and the interaction is spontaneous. The number of binding site and binding constant is 1 and 4.6×10⁴ (L/mol), respectively, which were increased in the presence of glucose. The presence of metallic ions and basic pH decreased the binding constant of nicotinamide to albumin. The obtained results indicated that nicotinamide tend to binds to the similar sites wherever the molecules with acidic moieties bind. The results could be helpful to interpret the mechanisms of actions of nicotinamide in the various physiological phenomena in the human body.

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This study aimed to identify PGP and MRPA genes in clinical isolates of Leishmania. The genes of pgpa (MRPA) and mdr1 (PGP) are involved in the drug resistance, their products act as dependent transporters of ATP (ABC Transporter) in the reflux of drugs from the cytosol to the outer space of the cell. Hence, 40 volunteers with leishmaniasis were randomly selected. Firstly, Amastigotes were examined under a light microscope, then inoculated into NNN-specific biphasic culture medium. Deoxy ribonucleic acids were extracted by phenol-chloroform method and were determined by ITS-specific primers. Then the frequency of two pumps involved in "drug resistance" was investigated by PCR. In this study, the mdr1 gene, which had previously been shown to be present in the in vitro resistant strains, was shown to have a higher frequency of pgpas, which could be due to the presence of MDR. It transports the drug from the inner layers of the lipid bilayer membrane to the outer layers, reducing the concentration of the drug inside the cell and causing drug resistance, while the MRPA pump is in the membrane of the cell organelles.

 

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Cisplatin, as a chemotherapy drug, causes serious side effects in the advanced stages of the cancer. Recently, Artemisia has been considered for its bioactive compounds, anti-proliferative and anti-inflammatory effects. The aim of this study was to evaluate the anti-cancer and anti-metastatic effects of the methanolic extract of aerial organs of Artemisia and cisplatin, either alone or in combination, in human ovarian cancer cell line A2780. The viability of A2780 cells after treatment with Artemisia extract, cisplatin and their combination was evaluated by MTT assay and the alterations in the morphology of the cell nuclei were examined by DAPI staining. The induction of apoptosis was assessed by Annexin V test, cell migration and changes in expression levels of apoptotic genes (Bax and P53) and metastasis (MMP2 and MMP9) using real-time PCR. MTT test data showed that Artemisia extract, cisplatin and their combination decreased the viability of ovarian cancer cells. DAPI and Annexin V indicated the DNA fragmentation and increased percentage of cellular apoptosis in comparison with the control group. The migration and real-time PCR data showed a decline in thr cell invasion and expression of genes involved in metastasis (MMP2 and MMP9) in cancer cells while the expression of apoptotic genes (Bax and P53) was increased in the treated groups. The results of this study showed that while both Artemisia extract and cisplatin posses anti-proliferative effect, apoptotic and suitable anti-metastatic effects on their own in A2780 cell line, their combination have synergic effects and posses those desired properties in lower concentration of cisplatin, which can reduce the side effects of cisplatin in cancer treatment.

 

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Pancreatic cancer is one of the most deadly and aggressive cancers; Fluorouracil induces apoptosis and cell cycle arrest in cancer cells. In the present study; the effect of Fluorouracil on different stages of the cell cycle and the expression of genes involved in the internal pathway of apoptosis in the AsPC-1 cell line (human pancreatic cancer) were investigated. In order to do so, MTT assay was used to evaluate the cytotoxic effect of Fluorouracil on AsPC-1 cell proliferation; The type of induced cell death and cell cycle changes were investigated by flow cytometry; changes in the expression level of genes (BAX, Bcl-2, APAF-1, Caspase-3, Caspase-9, p53, p21) were examined by Real-time PCR. Quantitative data were analyzed at the significant level of (p<0.05). The MTT assay results showed that Fluorouracil decreased AsPC-1 cell proliferation in a concentration-dependent manner. The results of flow cytometry analysis showed that increased percentage of apoptotic cells in the treated cells; Fluorouracil induces S phase cell cycle arrest in AsPC-1 cells and reduced distribution in the G1 phase. The Real-time PCR results in treated cells showed an increase in the expression of genes in the mitochondrial apoptotic pathway as well as genes effective in regulating the cell cycle. Fluorouracil reduces cell proliferation and induces apoptosis by increasing the expression of genes involved in the Intrinsic apoptotic pathway in AsPC-1 cells; Fluorouracil also caused cell cycle arrest in these cells by regulating the (p53, p21) genes.
 

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It has been found that the second isoform of COX enzyme known as COX-2 plays an important role in inflammation and rheumatoid arthritis and osteoarthritis. Thus, designing COX-2 inhibitors to treat inflammation is among the most important goals of researchers. In this study, the inhibitory effect of 3 new imidazole derivatives on COX-2 was evaluated by in silico approach. Molecular docking was done using Autodock Vina and the best binding mode of inhibitors was used as input of molecular dynamics (MD) simulation. MD was performed using Gromacs software for 120 ns. Then, structural and thermodynamic analyzes (ΔG_binding) and prediction of physicochemical properties were performed. RMSD data showed the compounds reached a good equilibrium and had favorable stability during simulation. Also, the RMSF showed that due to binding of inhibitors, the fluctuations of complexes decreased and the active site residues had the lowest amount. Rg, SASA and DSSP analysis showed that the protein structure did not change significantly. It was also found that Ser530 and Tyr355 residues play a more effective role in hydrogen bond formation. Physicochemical parameters determined the good drug-likeness properties for all compounds. Structural and thermodynamic analyzes (MM-PBSA) and IC₅₀ data indicate the favorable inhibitory effect of compound 5b.