Coumarins are the most important class of natural compounds found widely in various plants. Many coumarin derivatives with different biological and pharmacological activities have been synthesized. In this study, the antiapoptotic and cytotoxic effects and DNA-binding properties of some synthetic coumarin derivatives (4b, 4d, 4f, 4 g (DBP-g), 4 h and 4j) against K562 cell lines were investigated using different techniques. MTT assay indicated that the DBP-g compound was more active than other derivatives, with a IC 50 value of 55 μM, and therefore this compound was chosen for further investigation. Apoptosis induction was assessed using acridine orange/ethidium bromide double-staining and cell-cycle analysis. In addition, in vitro DNA-binding studies were carried out using ultraviolet-visible light absorption and fluorescence spectroscopy, as well as viscosity measurement and molecular modelling studies. In vitro results indicated that DBP-g interacted with DNA through a groovebinding mode with a binding constant (K b ) of 1.17 × 10 4 M −1 . In agreement with other experimental data, molecular docking studies showed that DBP-g is a minor groove binder. Overall, it can be concluded that DBP-g could be used as an effective and novel chemotherapeutic agent.

In this study, the effect of sub-minimum inhibitory concentrations of the zinc oxide nanoparticle on the expression of the α-haemolysin gene as a significant virulence factor of Staphylococcus aureus is assessed. The effect of sub-minimum inhibitory concentration (312.5 μg/ml) of the zinc oxide nanoparticle on the haemolysis phenomenon was studied phenotypically on blood agar media with and without zinc oxide nanoparticles and genetically by real time polymerase chain reaction method in media containing and without zinc oxide. The haemolysis phenomena of all S. aureus isolates in a blood agar with a sub-minimum inhibitory concentration and 1/2, 1/4 and 1/8 minimum inhibitory concentration of zinc oxide nanoparticles was completely restrained. After performing real time polymerase chain reaction, the amount of hla gene expression in 12 h culture in media with 1/2 and 1/4 minimum inhibitory concentration of zinc oxide nanoparticles was reduced, but gene expression in the 1/8 minimum inhibitory concentration was did not decrease. Haemolysis by S. aureus was decreased in the presence of sub-minimum inhibitory concentration of zinc oxide nanoparticles. The use of zinc oxide nanoparticle in sub-minimum inhibitory concentration as cover of artificial instruments such as catheter, intravascular catheters or shunts to control bacterial infection is suggested for further study.

Leishmaniasis is a vector-borne disease in tropical and subtropical regions. It presents a wide spectrum of clinical manifestations; Cutaneous Leishmaniasis (CL) is the most common form leading to a skin nodule. L-Arginine (L-Arg) is an important amino acid involved in many metabolic pathways in host macrophages (MΦs) including NO synthesis. The L-Arg pathway is relevant to leishmaniasis due to its role in regulating MΦ functions. Activated MΦs can produce leishmaniacidal molecules, such as Nitric Oxide (NO) and oxidative mediators to kill parasite. Different concentrations of L-Arg were used; their toxicities assessed in naïve Balb/c mice. The highest concentration with lowest toxicity was selected to apply in Leishmania major infected mice. Test group was injected with three types of L-Arg (oral, local, injection) and control group received normal saline. Then, the lesion size, the measurement of amastigotes proliferation in MΦ, the pathophysiology of mice (hepato/spelenomegaly, survival rate, body weight) was all evaluated. In addition, plasma and tissue suspensions were investigated for NO induction using Griess Micro Assay (GMA). This is the first application of oral, local and injection forms of L-Arg against Iranian strain L. major MRHO/IR/75/ER. Results indicated L-Arg had ability to elevate NO in murine host. No pathological effects were observed in oral, local and injection types of L-Arg. Moreover, a significant decrease in parasite proliferation was observed only in oral group which presented anti-leishmanial activity by reduction liver and spleen positive smears. In injection form, percentage of positive smears was reduced only in spleen; a reduction observed in lesion sizes after treatment with oral and injection form of L-Arg; no significant alteration of local L-Arg to limit lesion size in CL was indicated here. The L-Arg is NO precursor and has been used safely for decades to treat physiological condition and used as food supplementary with no toxicity. In this study, L-Arg presented its partial ability to induce NO and treat animals. It also has limited potential therapeutic effects against CL by alteration of NO in host; therefore, it may be indicated solo as an anti-leishmanial agent or in a combination therapy for CL in mice. This may be the first immunotherapy trial against CL in Iran.

Objectives Multiple sclerosis (MS) is a chronic disease of the central nervous system. The pathogenesis of MS is best described by a multifactorial model incorporating interactions between genetic and environmental factors with the role of genetic factors increasingly taken into account. The main goal of this study was to investigate the associations of rs12487066, rs12044852, rs10735781, rs3135388, rs6897932, rs1321172, rs10492972, and rs9657904 polymorphisms with MS in the Iranian population. Methods A total of 83 patients with MS (82.0% female and 18.0% male; mean age = 35.2±8.6 years) and 100 physically and mentally healthy subjects (81.0% female and 19.0% male; mean age = 40.4±6.4 years) were selected using convenient sampling. A 5 mL blood sample was taken from each case and control patient. We used the tetra-primer ARMS-PCR method to genotype the desired polymorphisms. The associations between polymorphisms and the disease were studied based on codominant, dominant, recessive, and overdominant models. Results The rs10735781 polymorphism was codominantly ( p = 0.029), overdominantly ( p = 0.008), and dominantly ( p = 0.009) associated with the disease. The rs6897932 was also found to be codominantly ( p = 0.012), dominantly ( p = 0.019), and recessively ( p = 0.011) associated with the disease. Conclusions We found an association between the rs10735781 and rs6897932 polymorphisms on the EVI5 and IL7RA genes, respectively, with increased MS in the Iranian population. Therefore, single nucleotide polymorphisms in the EVI5 and IL7RA genes can be considered a prognostic marker of MS.

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