Synthesis,cytotoxic evaluation and molecular docking study of 2-alkylthio-4-(2,3,4-trimethoxyphenyl)-5-aryl-thiazoles as tubulin polymerization inhibitors

A series of cis-restricted 2-alkylthio-4-(2,3,4-trimethoxyphenyl)-5-aryl-thiazole analogues of combretastatin A-4 were synthesized and investigated for inhibition of cell proliferation against three cancer cell lines, HT-29, MCF-7, and AGS, and a normal mouse fibroblastic cell line, NIH-3T3, using an MTT assay. The biological study showed that 2-(methylthio) substituted compounds showed little cytotoxic activity against the four cell lines. In contrast, the presence of the 2-(benzylthio) group on the thiazole ring resulted in a significant improvement in cytotoxic activity relative to the 2-(methylthio) substituted derivatives. Furthermore, the inhibition of tubulin polymerization by some potent compounds was evaluated. All the compounds studied were moderate tubulin polymerization inhibitors. The flow cytometry analysis confirmed that the synthesized compounds led to cell cycle arrest at the G₂/M phase. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model.     

Aflatoxin contamination of wheat flour and the risk of esophageal cancer in a high risk area in Iran

Background: Golestan province in northeastern Iran has been known as a high-risk area for esophageal cancer (EC). This study was conducted to assess aflatoxin (AF) contamination of wheat flour (WF) samples in high and low EC-risk areas of Golestan province. Methods: Four WF samples were collected randomly from each of 25 active silos throughout the province in 2009. The levels of AFs were measured using the High-performance liquid chromatography method. Using the data of EC rates obtained from Golestan population-based cancer registry, the province was divided into high and low risk areas for EC. Student t-test and multivariate regression analysis were used to compare the levels of aflatoxins as well as the condition of silos between the two areas. Results: One hundred WF samples were collected. The mean levels of total aflatoxin and aflatoxin B1 was 1.99 and 0.53 ng g^?1, respectively. The levels of total AF (p = 0.03), AFG2 (p = 0.02) and AFB1 (p = 0.003) were significantly higher in samples obtained from high risk area. Multivariate regression analysis showed that humidity of silo was the most important source of difference between silos of the two areas (p = 0.04). Conclusion: We found a positive relationship between AF level of WF samples and the risk of EC. So, AF contamination may be a possible risk factor for EC in our region. We also found that humidity of silos was the most important determinant of AF contamination of WF. Intensive control of silos conditions including humidity and temperature are needed especially in high EC-risk areas.     

Pulses of somatostatin release are slightly delayed compared with insulin and antisynchronous to glucagon

It was early proposed that somatostatin-producing delta-cells in pancreatic islets have local inhibitory effects on the release of insulin and glucagon. Recent observations that pulses of insulin and glucagon are antisynchronous make it important to examine the temporal characteristics of glucose-induced somatostatin release. Analysis of 30 s fractions from the perfused rat pancreas indicated that increase of glucose from 3 to 20 mmol/l results in initial suppression of somatostatin release followed by regular 4-5 min pulses. During continued exposure to 20 mmol/l glucose, the pulses of somatostatin overlapped those of insulin with a delay of 30 s. Somatostatin and glucagon pulses were coupled in antisynchronous fashion (phase shift 2.4+/-0.2 min), supporting the idea that the delta-cells have a local inhibitory effect on glucagon release. It was possible to remove the pulses of somatostatin and glucagon with maintenance of the insulin rhythmicity by addition of 1 micromol/l of the P2Y(1) receptor antagonist MRS 2179.     

Community knowledge and practices regarding malaria and long-lasting insecticidal nets during malaria elimination programme in an endemic area in Iran

A literature review for operational research on malaria control and elimination was conducted using the term 'malaria' and the definition of operational research (OR). A total of 15 886 articles related to malaria were searched between January 2008 and June 2013. Of these, 582 (3.7%) met the definition of operational research. These OR projects had been carried out in 83 different countries. Most OR studies (77%) were implemented in Africa south of the Sahara. Only 5 (1%) of the OR studies were implemented in countries in the pre-elimination or elimination phase. The vast majority of OR projects (92%) were led by international or local research institutions, while projects led by National Malaria Control Programmes (NMCP) accounted for 7.8%. With regards to the topic under investigation, the largest percentage of papers was related to vector control (25%), followed by epidemiology/transmission (16.5%) and treatment (16.3%). Only 19 (3.8%) of the OR projects were related to malaria surveillance. Strengthening the capacity of NMCPs to conduct operational research and publish its findings, and improving linkages between NMCPs and research institutes may aid progress towards malaria elimination and eventual eradication world-wide.     

Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions

In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm–MAA–HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.     

Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering

The combination of bioceramics and stem cells has attracted the interest of research community for bone tissue engineering applications. In the present study, a combination of Bio-Oss^® and type 1 collagen gel as scaffold were loaded with human adipose-tissue derived mesenchymal stem cells (AT-MSCs) after isolation and characterization, and the capacity of them for bone regeneration was investigated in rat critical size defects using digital mammography, multi-slice spiral computed tomography imaging and histological analysis. 8 weeks after implantation, no mortality or sign of inflammation was observed in the site of defect. According to the results of imaging analysis, a higher level of bone regeneration was observed in the rats receiving Bio-Oss^®-Gel compared to untreated group. In addition, MSC-seeded Bio-Oss-Gel induced the highest bone reconstruction among all groups. Histological staining confirmed these findings and impressive osseointegration was observed in MSC-seeded Bio-Oss-Gel compared with Bio-Oss-Gel. On the whole, it was demonstrated that combination of AT-MSCs, Bio-Oss and Gel synergistically enhanced bone regeneration and reconstruction and also could serve as an appropriate structure to bone regenerative medicine and tissue engineering application.     

The effect of sub-lethal exposure to copper and the time course of recovery in clean water on biochemical changes in juvenile fish (Acipenser persicus)

This study reports the 96-h LC₅₀ value and tissue copper (Cu) levels and biochemical changes in juvenile fish (Acipenser persicus) exposed to 0.026?mg/l ambient Cu for 1, 7 and 14?days. It then examined the recovery of the same parameters after placing the juvenile fish in clean water for a further period of 28?days. The intestine, kidney and gill Cu levels, plasma glucose, total protein, triglyceride, cortisol, triiodothyronine and thyroxine concentrations, liver protein contents, liver catalase, superoxide dismutase (SOD) and glutathione S-transferase activities were studied. The 96-h LC₅₀ value of Cu was 0.502?mg/l for juvenile A. persicus. The results indicate that Cu exposure produced significant accumulations of Cu in gills and kidney over the treatment time. Sublethal dose of Cu resulted in a short-term increase in plasma glucose, total protein and cortisol levels that decreased with time. After the 28-day recovery phase, there were significant differences in kidney Cu levels and triglyceride concentrations as well as SOD activities between recovery fish treatments and their control groups on day 42. The 28-day recovery phase caused significant decreases in total protein levels and SOD activities of Cu-exposed fish on day 42 compared to day 14. The results suggest that 28?days are insufficient for complete recovery to Cu exposure by juveniles and a longer period would be required for full recovery. Moreover, the study showed that the recovery phase following Cu exposure could change biochemical parameters to levels that are not close to those seen during exposure or control levels.     

Antifungal chitinases from <Emphasis Type="Italic">Bacillus pumilus</Emphasis> SG2: preliminary report

A halotolerant bacterium capable of chitinase production was previously isolated from saline soils of Gavkhooni marsh, Iran. The strain was identified as Bacillus pumilus strain SG2. This strain secretes two chitinases into the medium in response to the presence of chitin in the medium. The two chitinases, ChiS and ChiL, were active on both polymeric as well as oligosaccharide substrates. In this study, these two extracellular chitinases were purified from the supernatant of the Bacillus culture by ammonium sulfate precipitation. The optimum pH and temperature for both of these chitinases were pH 6 and 37°C, respectively. According to the conserved domain analysis, ChiS and ChiL were categorized in family 18 of the glycosylhydrolases. Three essential conserved amino acid residues (Asp-194, Asp-196 and Glu-198) in ChiS and (Asp-228, Asp-230 and Glu-232) in ChiL were found within the active site. Antifungal activities of the two purified chitinases were assessed on Rhizoctonia solani, Verticillium sp., Nigrospora sp., Stemphyllium botryosum and Bipolaris sp. demonstrating inhibition of all the tested strains. However, these chitinases did not inhibit cell wall formation of the non-chitin-containing fungi (oomycetes) Phytophthora citricola and Phytophthora capsici. This is the first investigation demonstrating antifungal activity of chitinases purified from B. pumilus SG2.     

Expression of Acyl-lipid △12-desaturase Gene in Prokaryotic and Eukaryotic Cells and Its Effect on Cold Stress Tolerance of Potato

We report the expression profile of acyl-lipid Δ12-desaturase (desA) gene from Synechocystis sp. PCC6803 and its effect on cell membrane lipid composition and cold tolerance in prokaryotic (Escherichia coli) and eukaryotic (Solanum tuberosum) cells. For this purpose, a hybrid of desA and reporter gene encoding thermostable lichenase (licBM3) was constructed and used to transform these cells. The expression of this hybrid gene was measured using qualitative (Petri dish test, electrophoregram and zymogram) and quantitative methods (spectrometry and gas liquid chromatography assays). The maximum level of linoleic acid in the bacterial cells containing hybrid gene was 1.9% of total fatty acids. Cold stress tolerance assays using plant damage index and growth parameters showed that cold tolerance was enhanced in primary transgenic lines because of increased unsaturated fatty acid concentration in their lipids. The greatest content of 18:2 and 18:3 fatty acids in primary transgenic plants was observed for lines 2 (73%) and 3 (41%). Finally, our results showed that desaturase could enhance tolerance to cold stress in potato, and desaturase and lichenase retain their functionality in the structure of the hybrid protein where the enzymatic activity of target gene product was higher than in the case of reporter lichenase gene absence in the construction.