Design and Synthesis of a Peptidyl-FRET Substrate for Tumor Marker Enzyme human Matrix Metalloprotease-2 (hMMP-2)

Matrix metalloproteases (MMPs) in particular MMP-2, have been associated with several pathological conditions such as ovarian, urothelial, cutaneous, gastric, breast, and cervical cancers, etc. Successful treatment of these pathological conditions requires sensitive, reliable, quick and effective diagnostic tools such as fluorescence resonance energy transfer (FRET) based assays in early stage of the disease. A peptidyl-FRET substrate having seven amino acid residues (PLGLKAR) with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher group has been synthesized using solid-phase fluorenylmethoxycarbonyl (Fmoc) peptide chemistry. The newly designed substrate is stable and shows a K _m value of 15???M for hMMP-2. This K _m value is the lowest compared with all other known hMMP-2 substrates having Mca/Dnp. Validation of the new FRET substrate in presence/absence of scorpion venom chlorotoxin, a known hMMP-2 inhibitor, shows an increase in detection efficiency of 6,250 times as compared to commonly used gelatin zymography. The new FRET substrate is much more cost effective and can be used for high throughput screening of hMMP-2 inhibitors in the laboratory for research and diagnostic purposes.     

Precise two-dimensional D-bar reconstructions of human chest and phantom tank via sinc-convolution algorithm

ABSTRACT: BACKGROUND: Electrical Impedance Tomography (EIT) is used as a fast clinical imaging technique formonitoring the health of the human organs such as lungs, heart, brain and breast. Eachpractical EIT reconstruction algorithm should be efficient enough in terms of convergencerate, and accuracy. The main objective of this study is to investigate the feasibility of preciseempirical conductivity imaging using a sinc-convolution algorithm in D-bar framework. METHODS: At the first step, synthetic and experimental data were used to compute an intermediate objectnamed scattering transform. Next, this object was used in a 2-day integral equation whichwas precisely and rapidly solved via sinc-convolution algorithm to find the square root of theconductivity for each pixel of image. For the purpose of comparison, multigrid and NOSERalgorithms were implemented under a similar setting. Quality of reconstructions of syntheticmodels was tested against GREIT approved quality measures. To validate the simulationresults, reconstructions of a phantom chest and a human lung were used. RESULTS: Evaluation of synthetic reconstructions shows that the quality of sinc-convolutionreconstructions is considerably better than that of each of its competitors in terms ofamplitude response, position error, ringing, resolution and shape-deformation. In addition, theresults confirm near-exponential and linear convergence rates for sinc-convolution andmultigrid, respectively. Moreover, the least degree of relative errors and the most degree oftruth were found in sinc-convolution reconstructions from experimental phantom data.Reconstructions of clinical lung data show that the related physiological effect is wellrecovered by sinc-convolution algorithm. CONCLUSIONS: Parametric evaluation demonstrates the efficiency of sinc-convolution to reconstruct accurateconductivity images from experimental data. Excellent results in phantom and clinicalreconstructions using sinc-convolution support parametric assessment results and suggest thesinc-convolution to be used for precise clinical EIT applications.     

Tamoxifen Induces Apoptosis of Leishmania major Promastigotes in Vitro

Tamoxifen is an antagonist of the estrogen receptor and currently used for the treatment of breast cancer. The current treatment of cutaneous leishmaniasis with pentavalent antimony compounds is not satisfactory. Therefore, in this study, due to its antileishmanial activity, effects of tamoxifen on the growth of promastigotes and amastigotes of Leishmania major Iranian strain were evaluated in vitro. Promastigotes and amastigotes were treated with different concentrations (1, 5, 10, 20, and 50 μg/ml) and time periods (24, 48, and 72 hr) of tamoxifen. After tamoxifen treatment, MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5 biphenyl tetrazolium bromide assay) was used to determine the percentage of live parasites and Graph Pad Prism software to calculate IC₅₀. Flow cytometry was applied to investigate the induction of tamoxifen-induced apoptosis in promastigotes. The half maximal inhibitory concentration (IC₅₀) of tamoxifen on promastigotes was 2.6 μg/ml after 24 hr treatment. Flow cytometry analysis showed that tamoxifen induced early and late apoptosis in Leishmania promastigotes. While after 48 hr in control group the apoptosis was 2.0%, the 50 µg/L concentration of tamoxifen increased it to 59.7%. Based on the in vitro antileishmanial effect, tamoxifen might be used for leishmaniasis treatment; however, further researches on in vivo effects of tamoxifen in animal models are needed.     

Trends in accumulation of ephedrine in callus cultures of <Emphasis Type="Italic">Ephedra major</Emphasis> Host

Ephedra major Host, a medicinal plant, belongs to the family of Ephedraceae. Ephedrine is the main alkaloid in Ephedra, which has different medicinal properties. However, the amount of ephedrine in plant material is low and callus culture can be a way to increase the alkaloid content. The aim of this research was to compare Murashige and Skoog (MS) and Gamborg’s B5 culture media for callus induction and ephedrine production. For this purpose, stem explants were cultured on MS or B5 media containing 0.0, 0.5, 1.0, 2.0, or 3.0 mg L^?1 of kinetin (Kin) either alone or in combination with 0.0, 0.5, 1.0, or 2.0 mg L^?1 2,4-dichlorophenoxyacetic acid (2,4-D) and/or naphthalenacetic acid (NAA), in five replicates. MS medium containing 1.0 or 2.0 NAA and 0.5 mg L^?1 Kin were the most effective for callus induction. The highest percentage of callus induction (100%) on B5 culture medium was obtained with 2.0 2,4-D and 0.5 mg L^?1 Kin treatments. The results showed that there was no significant difference between MS and B5 media for callus induction, and fresh and dry weight production. High-performance liquid chromatography was conducted for the identification and quantification of ephedrine in the obtained callus. The highest level of ephedrine (7.38 mg g^?1 DW) was found in callus grown on MS medium containing 0.5 mg L^?1 of 2,4-D. The results revealed that ephedrine can accumulate in callus cultures to levels much higher than in E. major wild plants.     

Length–weight and length–length relationships for two gobiids from the Anzali Wetland,in the southern Caspian Sea basin

Length–weight (LWR) and length–length (LLR) relationships were estimated for specimens of two gobiid species collected from the Anzali Wetland and its related streams in the southern Caspian Sea basin, in August 2017. These represent the first reports of LWR and LLR data for Rhinogobius cf. similis Gill, 1859 (37°28′13″N, 49°20′33″E; 50 individuals) and Proterorhinus nasalis (De Filippi, 1863) (36°54′10.89″N, 53°48′48.33″E; 30 individuals) from the Wetland. A new maximum length is reported for P. nasalis. The length–weight parameter b for these species ranged a minimum of 2.99 for Rhinogobius cf. similis to a maximum of 3.04 for P. nasalis with regression coefficients (r²) ranging from .95 to .97. All LLRs were highly significant (r²>.96).     

Oxidative stress‐induced renal telomere shortening as a mechanism of cyclosporine‐induced nephrotoxicity

Due to the association of oxidative stress and telomere shortening, it was aimed in the present study to investigate the possibility whether cyclosporine‐A exerts its nephrotoxic side effects via induction of oxidative stress‐induced renal telomere shortening and senescent phenotype in renal tissues of rats. Renal oxidative stress markers, 8‐hydroxydeoxyguanosine, malondialdehyde, and protein carbonyl groups were measured by standard methods. Telomere length and telomerase activity were also evaluated in kidney tissue samples. Results showed that cyclosporine‐A treatment significantly (P < 0.05) enhanced renal malondialdehyde, 8‐hydroxydeoxyguanosine, and protein carbonyl groups levels, decreased renal telomere length, and deteriorated renal function compared with the controls. Renal telomerase activity was not affected by cyclosporine‐A. Renal telomere length could be considered as an important parameter of both oxidative stress and kidney function. Telomere shortening and accelerated kidney aging may be caused by cyclosporine‐induced oxidative stress, indicating the potential mechanism of cyclosporine‐induced nephrotoxicity.     

A novel real-time driving fatigue detection system based on wireless dry EEG

Development of techniques for detection of mental fatigue has varied applications in areas where sustaining attention is of critical importance like security and transportation. The objective of this study is to develop a novel real-time driving fatigue detection methodology based on dry Electroencephalographic (EEG) signals. The study has employed two methods in the online detection of mental fatigue: power spectrum density (PSD) and sample entropy (SE). The wavelet packets transform (WPT) method was utilized to obtain the \(\theta \) (4–7 Hz), \(\alpha \) (8–12 Hz) and \(\beta \) (13–30 Hz) bands frequency components for calculating corresponding PSD of the selected channels. In order to improve the fatigue detection performance, the system was individually calibrated for each subject in terms of fatigue-sensitive channels selection. Two fatigue-related indexes: (\(\theta +\alpha \))/\(\beta \) and \(\theta \)/\(\beta \) were computed and then fused into an integrated metric to predict the degree of driving fatigue. In the case of SE extraction, the mean of SE averaged across two EEG channels (‘O1h’ and ‘O2h’) was used for fatigue detection. Ten healthy subjects participated in our study and each of them performed two sessions of simulated driving. In each session, subjects were required to drive simulated car for 90 min without any break. The results demonstrate that our proposed methods are effective for fatigue detection. The prediction of fatigue is consistent with the observation of reaction time that was recorded during simulated driving, which is considered as an objective behavioral measure.     

Role of lung inflammatory mediators as a cause of exercise-induced arterial hypoxemia in young athletes.

We examined whether lung inflammatory mediators are increased during exercise and whether pharmacological blockade can prevent exercise-induced arterial hypoxemia (EIAH) in young athletes. Seventeen healthy athletes (9 men, 8 women; age 23 +/- 3 yr) with varying degrees of EIAH completed maximal incremental treadmill exercise tests after administration of fexofenadine, zileuton, and nedocromil sodium or placebo in a randomized double-blind crossover study. Lung function, arterial blood gases, and inflammatory metabolites in plasma, urine, and induced sputum were assessed. Drug administration did not improve EIAH or gas exchange during exercise. At maximal exercise, oxygen saturation fell to 91.4 +/- 2.6% (drug trial) and 91.9 +/- 2.1% (placebo trial) and alveolar-arterial oxygen difference widened to 28.1 +/- 6.3 Torr (drug trial) and 29.3 +/- 5.7 Torr (placebo trial). Oxygen consumption, ventilation, and other exercise variables were similarly unaffected by drug treatment. Although plasma histamine increased with exercise, values did not differ between trials, and urinary leukotriene E(4) and 11beta-prostaglandin F(2alpha) levels were unchanged after exercise. Postexercise sputum revealed no significant changes in markers of inflammation. These results demonstrate that EIAH in young athletes is not attenuated with acute administration of drugs targeting histamine and bioactive lipids. We conclude that airway inflammation is of insufficient magnitude to cause impairments in gas exchange and does not appear to be linked to EIAH in healthy young athletes.