Low solubility and dissolution rate are the primary challenges in the drug development which substantially impact the oral absorption and bioavailability of drugs. Due to the poor water solubility, Albendazole (ABZ) is poorly absorbed from the gastrointestinal tract and shows low oral bioavailability (5%) which is a major disadvantage for the systemic use of ABZ. To improve the solubility and dissolution rate of ABZ, different classes of hydrophilic excipients such as sugars (lactose, sucrose, and glucose), polyols (mannitol and sorbitol), ionic surfactant (sodium lauryl sulfate) and non-ionic surfactant (Cremophor A25) were co-spray dried with ABZ. The crystallinity changes in the processed drug were characterized by differential scanning calorimetry and X-Ray diffraction methods were used to interpret the enhanced solubility and dissolution rate of the drug. Results showed that the solubility and dissolution rate of ABZ were increased 1.8-2.6 folds and 3-25 folds, respectively. Unexpectedly, SLS decreased the solubility index of drug powder even lower than the unprocessed drug which was attributed to drug-SLS ionic interaction as depicted from Fourier transform infrared spectroscopy. It was concluded that by applying the facile, one-step, industrially scalable technique and the use of small amounts of excipient (only 4% of the formulation), a great improvement (21 folds) in dissolution rate of ABZ was achieved. This finding may be used in the pharmaceutical industries for the formulation of therapeutically efficient dosage forms of class II and IV drugs classified in biopharmaceutical classification system.

In the current study, both ligand-based molecular docking and receptor-based quantitative structure activity relationships (QSAR) modeling were performed on 35 diaryl urea derivative inhibitors of ^V600E B-RAF. In this QSAR study, a linear (multiple linear regressions) and a nonlinear (partial least squares least squares support vector machine (PLS-LS-SVM)) were used and compared. The predictive quality of the QSAR models was tested for an external set of 31 compounds, randomly chosen out of 35 compounds. The results revealed the more predictive ability of PLS-LS-SVM in analysis of compounds with urea structure. The selected descriptors indicated that size, degree of branching, aromaticity, and polarizability affected the inhibition activity of these inhibitors. Furthermore, molecular docking was carried out to study the binding mode of the compounds. Docking analysis indicated some essential H-bonding and orientations of the molecules in the active site.

The present study was designed to study the preventive effect of hydroalcoholic extract of ripe pistachio hulls (RPH) in the elevated plus maze model of anxiety. One hundred twenty female wistar rats in their estrous cycle were divided into 15 groups of 8 each and received various concentrations of hydroalcoholic extract of RPH except the control groups. Elevated plus maze was used to measure the level of anxiety. Percentage of time spent in the open arms (%OAT), percentage of the number of entries into the open arms (%OAE), locomotor activity, and time spent in the closed arms (CAT), and the number of entries in to the closed arms (CAE) were measured and compared. Dose-response experiments showed that only 10 mg/kg dose of RPH extract significantly increased %OAT (P < 0.001) and %OAE (P < 0.05) compared to the control group, indicating anti-anxiety effects of the extract. Also, pentylenetetrazol and an estrogen receptor antagonist (ERA) tamoxifen could block anti-anxiety effects of the extract (P < 0.001). It was also noticed that tamoxifen was able to significantly reduce locomotor activity. As the RPH extract showed a preventive effect in experimental model of anxiety, it might be concomitantly administered with other anxiolytic medications.

Recombinant protein production in E. coli has several advantages over other expression systems. Misfolding, inclusion body formation, and lack of eukaryotic post translational modification are the most disadvantages of this system. Exporting of correctly folded proteins to the outside of reductive cytoplasmic environment through twin-arginine system could help to pass these limiting steps. Two signal sequences, TorA and SufI are used at N-terminal of human growth hormone (hGH) bearing DsbA gene sequence at C-terminal to enhance folding. The synthetic cassettes including the signal sequence, hGH and DsbA were transformed into E. coli BL21 (DE3) to study the effect of signal sequence and DsbA chaperone on translocation and folding of the protein. The results confirmed using signal sequence at N-terminal of targeted protein and coexpression with DsbA could transport proteins to the periplasmic space and culture media compared to control groups. Although there is no protein band of somatropin in SDS-Page of culture media samples when using SufI as signaling sequence, the study demonstrated TorA signal sequence could transport the target protein to the culture media. However, there was a considerable amount of hGH in periplasmic space when using SufI compared to control.

Lovastatin as a member of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is used as a lipid-lowering agent. It can also inhibit the formation of hydrogen peroxide and superoxide anion and finally leads to decline in oxidative stress processes. Here, we evaluated whether lovastatin can increase DNA damage resistance of HepG2 cells against genotoxicity of the anticancer drug bleomycin (BLM). HepG2 cells were incubated with different concentrations of lovastatin (0.1, 0.5, 1, 5 µM) before exposure to BLM (0.5 µg/mL for one h). The genotoxic dose of BLM and lovastatin was separately determined and comet assay was used to evaluate the genotoxicity. After trapping cells in agarose coated lames, they were lysed and the electrophoresis was done in alkaline pH, then colored and monitored by florescent microscope. The results of this study indicated that lovastatin in doses lower than 5 µM has genoprotective effect and in doses higher than 50 µM is genotoxic. In conclusion, lovastatin is able to protect genotoxic effects of BLM in HepG2 cells. Further studies are needed to elucidate the mechanism(s) involved in this process.

Several attempts have so far been made in the search of new anticancer agents of plant origin. Some studies have reported that different species of Pine genus possess cytotoxic activities against various cancer cell lines. In the present study, we evaluated the cytotoxic effects of Pinus eldarica bark and leaf extracts or leaf essential oil on HeLa and MCF-7 tumor cell lines. Hydroalcoholic and phenolic extracts and the essential oil of plant were prepared. Total phenolic contents of the extracts were measured using Folin-Ciocalteu reagent. Essential oil components were determined by gas chromatography-mass spectroscopy (GC-MS). Cytotoxic activity of the extracts and essential oil against HeLa and MCF-7 tumor cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The polyphenolic content of hydroalcoholic and phenolic extracts of the bark and hydroalcoholic extract of the leaf were 48.31%, 47.2%, and 8.47%, respectively. According to the GC-MS analysis, the major components of the leaf oil of P. eldarica were: ß -caryophyllene (14.8%), germacrene D (12.9%), α-terpinenyl acetate (8.15%), α -pinene (5.7%), and -α humulene (5.9%). Bark extracts and leaf essential oil of P. eldarica significantly reduced the viability of both HeLa and MCF-7 cells in a concentration dependent manner. However, leaf extract showed less inhibitory effects against both cell lines. The essential oil of P. eldarica was more cytotoxic than its hydroalcoholic and phenolic extracts. The terpenes and phenolic compounds were probably responsible for cytotoxicity of P. eldarica. Therefore, P. eldarica might have a good potential for active anticancer agents.

Sensitive skin is a frequently mentioned cosmetic complaint. Addition of a biomimetic of neuromediator has recently appeared as a promising new way to cure skin care product problems. This study was aimed to assess the inhibitory effect of a biomimetic lipopeptide derived from proopiomelanocortin (bPOMC) on capsaicin-induced sensory irritation in human volunteers and also to compare its protective effect with that of the well-known anti irritant strontium chloride. The effect of each test compound was studied on 28 selected healthy volunteers with sensitive skin in accordance with a double-blind vehicle-controlled protocol. From day 1 to day 13 each group was applied the test compound (bPOMC or strontium chloride) to one wing of the nose and the corresponding placebo (vehicle) to the other side twice daily. On days 0 and 14, acute skin irritation was induced by capsaicin solution and quantified using clinical stinging test assessments. Following the application of capsaicin solution, sensory irritation was evaluated using a 4-point numeric scale. The sensations perceived before and after treatment (on days 0 and 14) was calculated for the two zones (test materials and vehicle). Ultimately the percentage of variation between each sample and the placebo and also the inhibitory effect of bPOMC compared to that of strontium chloride were reported. Clinical results showed that after two weeks treatment, the levels of skin comfort reported in the group treated with bPOMC were significantly higher than those obtained in the placebo group and the inhibitory effect of bPOMC was about 47% higher than that of strontium chloride. The results of the present study support the hypothesis that biomimetic peptides may be effective on sensitive skin.

Preterm contraction of uterus is a main cause of miscarriages and preterm labour. Euphorbia known as Ferphion in Iranian traditional medicine texts like Al-Hawi, is reported for prevention of preterm labour. Therefore, the objective of this research was to investigate the effect of Euphorbia spinidens Bornm. Ex Prokh. on motility of rat uterus. Uterine horns were isolated form non-pregnant female rats pretreated with estrogen. E. spinidens hydroalcoholic extract was examined on KCl (80 mM) induced and spontaneous periodic contraction in isolate uterine strips suspended in an organ bath and compared with nifedipine and ritodrine. In isolated rat uterine strips, E. spinidens extract (1-500 µg/mL) showed mixed effects. At lower concentrations, firstly potentiated the spontaneous periodic contraction, while in concentrations above 256 µg/mL the spontaneous periodic contractions were completely attenuated. These findings demonstrated that although lower concentrations of hydroalcoholic extract potentiated the spontaneous periodic contraction of rat uterine smooth muscle, but at higher concentrations it had inhibitory effect on rat uterus contraction.

Changes in the substitutions at C-3 and C-5 positions of 4-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine have led to changes in potency of the compounds. The objective of the present study was to examine the hypotensive effects of 5 newly synthesized dihydropyridine derivatives of nifedipine in rats with phenylephrine-raised blood pressure. Anesthetized Sprague-Dawley rats were randomly assigned to 19 groups of 7 animals each. Control group received the vehicle dimethylsulfoxide (0.05 mL), 3 groups were given nifedipine at 100, 300, or 1000 μg/kg, and 5 other groups each composed of 3 subgroups administered one of the 5 new dihydropyridine compound at 100, 300, or 1000 μg/kg. All animals were initially infused with 20 µg/kg/min phenylephrine for 45 min, and were then given a bolus of either dimethylsulfoxide, nifedipine, or new dihydropyridine compounds 20 min after the commencement of phenylephrine infusion. Blood pressure and heart rate (HR) of the animals were measured before and at the end of phenylephrine infusion, or 25 min after injection of vehicle or compounds. Compared to dimethylsulfoxide, nifedipine, and new 1, 4-dihydropyridine derivatives caused significant reductions in MBP. Moreover, cyclohexyl propyl, phenyl butyl, and cyclohexyl methyl analogs of 1, 4-dihydro-2,6-dimethyl-4-(1-methyl-5-nitro-2-imidazoyl)-3,5-pyridinedicarboxylase at 100 μg/kg, phenyl butyl, and cyclohexyl methyl analogs at 300 μg/kg, and cyclohexyl methyl analogs at 1000 μg/kg reduced MBP similar to nifedipine. There was no significant difference between HR of all groups before and after administration of the compounds. The findings indicated that changes in substitution at C-3 and C-5 positions of 2-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine were associated with changes in hypotensive activity of the compounds.

In this study, we evaluated the effects of all-trans retinoic acid (ATRA) alone or in combination with genistein (GEN) in p14 tumor suppressor gene and subsequent apoptosis of human ovarian carcinoma cells (OVCAR-3). The cells were treated with ATRA or GEN at concentrations of 50 and 25 μM respectively, either alone or in combination for 24 and 48 h. The cell viability was evaluated using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. The percentage of cell apoptosis was determined using flow cytometry and p14 gene expression was measured using real time PCR. The MTT results showed that in both ATRA and GEN treated groups, the cell viabilityviability in group treated for 48 h was significantly lower than group treated for 24 h. The flow cytometry results showed that the percentage of apoptotic cells in groups that treated with ATRA and GEN in combination for 24 h and 48 h was significantly more than all other tested groups. The real time results showed that the mRNA level of p14 in cells treated with both drugs for 48 h was significantly higher than all other groups. In conclusion, we confirm that GEN in combination with ATRA is an effective strategy to up regulate the p14 tumor suppressor gene and induce cell apoptosis in OVCAR-3 cell line.