The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0.01nM-1 µM) alone or in combination with 50 nM of the CYP1A1 inhibitor 3'methoxy-4'nitro-flavone (MNF). CYP1A1 enzyme activity, cell viability, oxidative stress, and several endpoints of apoptosis were measured. FICZ treatment at a high concentration or in combination with MNF induced sustained CYP1A1 activity and led to oxidative stress and activation of apoptosis via a mitochondrial-dependent pathway. In comparison with the wild-type Hepa-1 cells, c37 cells lacking CYP1A1 activity proliferated faster in normal medium which contains trace levels of FICZ. Besides, in HepG2 cells, FICZ stimulated cell growth at low concentrations but inhibited cell growth at high concentrations. Based on these findings, we propose that CYP1A1 inhibitors, by increasing the levels of the endogenous ligand FICZ, change the cell growth kinetics and trigger cell death and apoptosis through a mitochondrial-dependent pathway. Since AHR controls multiple cellular functions, a wide range of toxicity can be expected by disturbing its endogenous functions.
Highly diastereoselective synthesis of chromeno β-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired β-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4hydroxycoumarin in the presence of 1,4-diazabicyclo[2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1 H NMR, 13 C NMR spectral data and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. β-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. β-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.
Rotavirus is the leading cause of acute gastroenteritis in worldwide young children. Effective vaccines to prevent rotavirus infection are currently available, although their clinical use is still limited, and rotavirus still causes many episodes of infantile gastroenteritis, mainly during the winter season. The aim of this study was to evaluate the prevalence of rotavirus infection in children aged \5-years-old who were hospitalised for gastroenteritis. One hundred and sixty-three stool samples from hospitalised children (\5-years-old) complicated with severe diarrhoea, in two hospitals in Jahrom City, Iran were collected from 2009 to 2010. Antigenic prevalence of rotavirus group A was distinguished by enzyme immunoassay. The antigen of group A rotavirus was diagnosed by EIA in 75 of 163 collected samples. The genotype of EIA-positive samples was determined by nested RT-PCR. The frequency of rotavirus genotypes G1, G2, G3, G4 and G9 was 17.33, 13.34, 2.67, 30.66 and 2.67 %, respectively. Also, the frequency of mixed and non-typable genotypes was detected in 2.67 and 30.66 %, respectively. G1/G8 mixed infection was the first of these rotavirus genotypes to be reported in Iran. Detection of high prevalence of group A rotavirus infection in hospitalised children with diarrhoea, and determination of circulating rotavirus genotypes in this region of Iran, provide useful data for formulating effective vaccines; especially for infants less than 5-years-old.
In this study, a new type of silver nanoparticles capped with metronidazolium based ionic liquid is synthesized. By this aim, metronidazole is altered to ionic-liquid type structure with citrate counter ion as reducing agent. The produced reducing agent was characterized using 1 HNMR and 13 CNMR and FT-IR. The capability of metronidazolium-based reducing agent in formation and capping silver nanoparticles was examined in a chemical reaction. More specifically, synthesized silver nanoparticles were synthesized and capped with metronidazoliumcitrate based ionic liquid, while the formation of particles in 48 h was monitored by UV-Vis spectroscopy. Fourier transform infrared spectroscopy showed the presence of capping agents around silver nanoparticles. The amount of metronidazolium and citrate as capping agents was determined by thermal gravimetric analysis. The prepared crystalline structure of silver nanoparticles was proved by X-ray diffraction spectroscopy. PSA analysis and TEM was performed to determine the size of particles. The synthesized silver nanoparticle has the potential to be used as an antibacterial agent in preparation of wound dressing with extra capability and efficacy in aerobic and anaerobic bacterium. In this regard, the antibacterial efficacy of discs from different concentration of silver nanoparticles in calcium alginate medium were evaluated in Gram-negative and Gram-positive bacterium.
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