Specificity of Calreticulin Transacetylase to acetoxy derivatives of benzofurans: Effect on the activation of platelet Nitric Oxide Synthase

Calreticulin Transacetylase (CRTAase) catalyzes the transfer of acetyl group(s) from polyphenolic acetates (PAs) to functional proteins, such as Glutathione S-transferase (GST), NADPH Cytochrome c reductase and Nitric Oxide Synthase (NOS) resulting in the modulation of biological activities. A comparison of the specificities of the acetoxy derivatives of coumarins, biscoumarins, chromones, flavones, isoflavones and xanthones has been carried out earlier by us with an aim to study the effect of nature and position of the acetoxy groups on the benzenoid ring and the position of the carbonyl group with respect to oxygen/nitrogen heteroatom for the catalytic activity of CRTAase. In this communication for the first time, we have studied the influence of differently substituted benzofurans on the CRTAase activity to study the effect of the replacement of pyran ring of coumarin with furan ring, presence of carbonyl at C-3, substitution of C-3 carbonyl group with acetoxy group and presence of various substituents (OAc/OH/Cl) on the benzenoid ring. It was observed that acetoxy derivatives of benzofurans lead to inhibition of ADP induced platelet aggregation by the activation of platelet Nitric Oxide Synthase catalyzed by CRTAase. Accordingly, the formation of NO in platelets by 3-oxo-2,3-dihydrobenzofuran-6,7-diyl diacetate (3a) was found to be comparable with that of model polyphenolic acetate (PA), 7,8-diacetoxy-4-methylcoumarin (DAMC).     

The effect of long-term exposures to hypersaline particles originated from drying Urmia hypersaline Lake on the increased cardiovascular risks in the villagers around the Lake

Abstract

Background and Objectives: The world’s second largest permanent hypersaline lake, Lake Urmia, is drying in recent years and the dried bed of the Lake acts as a hypersaline particle emission source. Therefore, we aim to evaluate (for the first time to our knowledge) the association between hypersaline particles and biomarkers of inflammation and coagulation (hs-CRP and fibrinogen) in the residents around the Lake Urmia.

Methods: Three regions were selected as clean (region No.1) and polluted regions (region No.2 and No.3) for ambient particulate matter around the Urmia Lake from 2008 to 2015. In order to confirm the selected regions concentration of APM was measured in the selected regions for six months. Totally 123 participants were selected randomly, fibrinogen, hs-CRP and covariates were measured in the selected regions and were analyzed using multiple linear regression models.

Results: We found a statistically significant association between the hypersaline particles and fibrinogen in both polluted regions. This is while an association between hypersaline particles and hs-CRP was significant only in the polluted region No.2.

Conclusions: These results are consistent with our hypothesis that long-term exposure to hypersaline particles originated from drying Urmia hypersaline Lake is related to increased levels of hs-CRP and fibrinogen.     

Cellular uptake and apoptotic properties of gemini curcumin in gastric cancer cells

Molecular Biology Reports - Curcumin is a polyphenolic natural compound, which has demonstrated to possess antioxidant, anti-inflammatory, and anticancer effects in vitro & in vivo....     

Phytosynthesis of poly (ethylene glycol) methacrylate-hybridized gold nanoparticles from C. tuberculata: their structural characterization and potential for in vitro growth in banana

In Vitro Cellular & Developmental Biology - Plant - Here, we are analyzing the comparative study of green-synthesized biogenic Caralluma tuberculata gold nanoparticles (Ca-AuNPs) and poly...     

Resistance of peripheral and sub-cortical somatosensory pathway to electrical noise

The somatosensory system is vulnerable to large amounts of noise distortion. But how does the central nervous system distinguish the peripheral inputs which carry information to the brain from that which does not possess information? To address this question we studied the effect of electrical stimulation of the median nerve on tactile spatial frequency perception in healthy subjects and Parkinson's disease (PD) patients. Subjects were categorized in two groups (healthy and PD patients) and were asked to report if a test tactile frequency pattern (TFP) was the same as the reference TFP given to the other hand. In each case stimulation was either present or absent on the median nerve of the hand holding the test pattern. We observed no impairment of tactile performance in the presence of electrical stimulation of the median nerve. This result together with previous work on direct stimulation of the somatosensory relay nucleus of the thalamus (Abbassian et al., Stereotact Funct Neurosurg 76: 19–28, 2001) in which the same result of no impairment of the tactile discrimination task was observed suggest a high degree of noise tolerance exists in the somatosensory pathway.     

Plasmodium vivax dhfr mutations among isolates from malarious areas of Iran

The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.     

Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents

A facile synthesis of model 4-oxopyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acids 9a-e was achieved via Stille arylation of 2-chloro-3-nitro-4-oxothieno[2,3-b]pyridine-5-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. Compounds 9a-c and 9e exhibited very high potency against Gram positive Bacillus subtilis and Bacillus megaterium at concentrations 0.000015-0.007 μg/mL. They also displayed excellent activity towards other Gram positive bacilli and staphylococci and Gram negative Haemophilus influenzae, being in most cases superior or equal to commercial fluoroquinolones. Both 9a and 9c were inhibitors of the DNA gyrase activity. As concerns antitumor properties, compounds 9b-e showed growth inhibition of MCF-7 breast tumor and A549 non-small cell lung cancer cells with IC(50) 1.6-2.8 μM and 2.6-6.9 μM, respectively, coupled with absence of cytotoxicity towards normal cells. These compounds are promising as dual acting chemotherapeutics.     

Upgrading activated sludge systems and reduction in excess sludge

Most of 200 Activated Sludge Plant in Iran are overloaded and as a result, their efficiency is low. In this work, a pilot plant is manufactured and put into operation in one of the wastewater treatment plants in the west of Tehran. Instead of conventional activated sludge, a membrane bioreactor and an upflow anaerobic sludge blanket reactor used as a pretreatment unit in this pilot. For the sake of data accuracy and precision, an enriched municipal wastewater was opted as an influent to the pilot. Based on the attained result, the optimum retention time in this system was 4h, and the overall COD removal efficiency was 98%. As a whole, the application of this retrofit would increase the plant's capacity by a factor of 5 and reducing the excess sludge by a factor of 10. The sludge volume index in the anaerobic reactor was about 12 after granulation occurred.     

Anticancer and cytotoxic effects of troxerutin on HeLa cell line: an in-vitro model of cervical cancer

Cervical cancer is one of the grave uterine tumors which leads to death in women worldwide. Troxerutin (TRX) as a bioflavonoid compound has many pharmacological effects such as anti-neoplastic, radioprotective, and anti-cancer. The present study was designed to examine the cytotoxic effect of TRX on human HeLa tumor cells. Human HeLa cells were cultured and treated with different doses of TRX (20–640?mg/ml) to evaluate the effective half-maximal inhibitory concentration (IC₅₀) after 24?h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used for cell proliferation assay. Also, the Bax, Bcl-2, cleaved caspase-3, and tumor necrosis factor-α (TNF-α) protein expression levels were detected with immunoblotting analysis. The malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured via their commercial kits. Data were analyzed using one-way ANOVA. The result showed that TRX at 320?mg/ml concentration (IC₅₀) has a growth inhibitory effect against HeLa cells at 24?h treatment (P???0.01). Moreover, it increased the MDA concentration and also decreased the GPx and SOD activity levels at 320?mg/ml concentration versus control (P?<?0.001). Also, TRX significantly up-regulated the Bax, cleaved caspase-3 and TNF-α proteins expression levels (P ?<??0.01) and down-regulated the Bcl-2 protein expression in HeLa tumor cells at 320?mg/ml concentration compared to control (P?<?0.05). Our study showed that 24?h of treatment with TRX (320?mg/ml) has apoptotic and growth inhibitory effects against HeLa cells. It can induce inflammation (at least via up-regulating the TNF-α protein expression) and oxidative stress in human HeLa cells.