ACE-Inhibitory and Antioxidant Activity of Temporin-Ra Peptide: Biochemical Characterization and Molecular Modeling Study

In this study, the inhibitory effect of Temporin-Ra (FP-14 peptide) on angiotensin converting enzyme (ACE) was evaluated. Inhibition mechanism was investigated by kinetic studies and molecular docking simulation. Lineweaver–Burk plot revealed that Temporin-Ra behaved as a non-competitive ACE inhibitor supported by the docking simulation. The IC₅₀ and K_i values were determined to be 22.19 μM and 36 µg/ml, respectively. Molecular docking simulation showed that Temporin-Ra bound to both of N- and C-domains of ACE by forming hydrogen bonds and electrostatic interactions; Temporin-Ra displayed higher affinity to C-domain than N-domain. Antioxidant activity of Temporin-Ra was examined using different methods. The antioxidant activity of Temporin-Ra (0.2 mg/ml) in the inhibition of linoleic acid autoxidation was evaluated to be 57 %. 1,1-diphenyl-2-picrylhydrazyl and 2, 2-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) diammonium salt radicals scavenging activities were 60 % at 0.5 mg/ml and 37 % at 0.3 mg/ml, respectively. The hydroxyl radical scavenging of FP-14 peptide at 0.33 mg/ml was 55 %. The results suggest that Temporin-Ra is a multifunctional peptide that could be exploited to develop new anti-hypertension drugs and bio-compatible natural antioxidants.     

Complexation of Group IIIA metals with asymmetric tridentate ligands: Synthesis, characterization, formation constants and cytotoxicity

A series of new aluminum(III), gallium(III) and indium(III) complexes with some tridentate Schiff base, viz., N-{pyridine-2-ylmethyl}-2-hydroxy-5-methoxy-benzylideneamine [HL¹], N-{pyridine-2-ylmethyl}-2-hydroxy-benzylideneamine [HL²], N-{pyridine-2-ylmethyl}-2-hydroxy-5-nitro-benzylideneamine [HL³], N-{pyridine-2-ylmethyl}-2-hydroxy-5-bromo-benzylideneamine [HL⁴], N-{pyridine-2-ylethyl}-2-hydroxy-5-methoxy-benzylideneamine [HL⁵], N-{pyridine-2-ylethyl}-2-hydroxy-benzylideneamine [HL⁶], N-{pyridine-2-ylethyl}-2-hydroxy-5-nitro-benzylideneamine [HL⁷], N-{pyridine-2-ylethyl}-2-hydroxy-5-bromo-benzylideneamine [HL⁸], with the general formula [ML₂][Y] (M = Al³⁺, Ga³⁺, In³⁺; Y = NO₃⁻, ClO₄⁻) were synthesised and characterized by elemental analysis, ¹H NMR, FT-IR, UV-Vis spectrophotometry and mass spectrometry. The thermodynamic formation constants of the complexes were determined spectrophotometrically at constant ionic strength (I = 0.10 M NaClO₄) and at 25 °C in methanol. The trend of formation constants of the complexes are as follow:

Al<Ga<In     

Profound destructive effects of adolescent exposure to vincristine accompanied with some sex differences in motor and memory performance

Vincristine, an anticancer drug, is known to induce neuronal cell damage. We have elucidated the alteration in performance of the hippocampus and cerebellum following chronic vincristine treatment (0.2?mg·(kg body mass)(-1)·week(-1)) in male and female rats. Intraperitoneal injection of vincristine in adolescent rats caused impairment of motor and cognitive behavior. In the probe test, the length of path traveled and percent swimming time for vincristine-treated rats in the correct quadrant was significantly less than for the saline-treated (control) groups. The path length and time latency at the 2nd and 3rd blocks of trials for the male vincristine-treated group was significantly higher than that for the female saline- and the vincristine-treated rats. In the rod test, vincristine exposure impaired the motor coordination in both male and female rats. Exposure to vincristine caused a significant decrease in hanging time in male rats, compared with the saline- and the vincristine-treated female rats, while there were no differences between the female vincristine-treated rats and the saline-treated rats of both sexes. The rearing frequency, total distance moved, and velocity for both male and female rats were dramatically affected by exposure to vincristine. We have observed that the hippocampal and cerebellar functions of male and female rats were profoundly affected by exposure to vincristine, especially the male rats, suggesting a sexual dimorphism in the developing central nervous system that is affected by chemicals such as anticancer drugs.     

Effects of green synthesis of sulfur nanoparticles from Cinnamomum zeylanicum barks on physiological and biochemical factors of Lettuce (Lactuca sativa)

Physiology and Molecular Biology of Plants - In this study, the effect of green synthesized sulfur nanoparticle (SNP) at different concentration (0, 0.01, 0.1, 1 and 10&nbsp;mg/ml) on some...     

Upregulation of Fucosyltransferase 3, 8 and protein O-Fucosyltransferase 1, 2 genes in esophageal cancer stem-like cells (CSLCs)

Recently, studies have shown that Fucosylation plays an important role in the invasion and metastatic process of CSLCs. Understanding the expression pattern of fucosyltransferase (FUT) genes may help to suggest better-targeted therapy strategies for esophageal squamous cell carcinoma (ESCC). The study aimed to address the expression pattern of FUT gene variants in esophageal CSLCs and parental adherent cells. Sphere formation method was used to enrich CSLCs. Expression of FUT genes was examined in tumor sphere and parental adherent cells using the RT-PCR method and then relative expression of detected variants was performed by the Real-Time PCR method in both groups. The detected FUTs, also, were assessed in fresh ESCC tumors and the matched healthy controls. Analysis of The cell surface carbohydrate Lewis x (LeX, CD15) was performed by flow cytometry. Molecular analysis showed that the expression of FUT 3, 8 and POFUT1, 2 genes in tumorsphere were significantly higher than parental adherent cells. Analysis of fresh ESCC tumor tissues and the matched healthy controls showed that FUT8 and POFUT1, 2 genes in contrast to FUT 3 have higher expression in tumor tissues than controls. Flow cytometric analyses revealed that tumorsphere and their parent cells do not differ significantly in Lewis x surface marker. The present study showed that FUT 3, 8 and POFUT1, 2 genes upregulated in esophageal CSLCs in comparison to adherent cells. Understanding the expression pattern of FUT gene variants may help to suggest better-targeted therapy strategies for ESCC.     

Enhancement of exopolysaccharide production from Ganoderma lucidum using a novel submerged volatile co-culture system

Based on the impact of volatile organic compounds (VOCs) on secondary metabolite pathways, a novel submerged volatile co-culture system was constructed, and the effects of thirteen fungal and bacterial VOCs were investigated on Ganoderma lucidum exopolysaccharides production. The results demonstrated at least a 2.2-fold increase in exopolysaccharide (EPS) specific production yield in 6 days submerged volatile co-culture of G. lucidum with Pleurotus ostreatus. Therefore, P. ostreatus was selected as a variable culture, and the effects of agitation speed, inoculum size, initial pH, and co-culture volume on EPSs production were investigated using a Taguchi L₉ orthogonal array. Finally, the highest concentration of EPSs (3.35 ± 0.22 g L^?1) was obtained under optimized conditions; initial pH 5.0, inoculum size 10%, 150 rpm, and 3:1 volume ratio of variable culture to main culture.     

Palmitate-activated macrophages confer insulin resistance to muscle cells by a mechanism involving protein kinase C θ and ε

Background

Macrophage-derived factors contribute to whole-body insulin resistance, partly by impinging on metabolically active tissues. As proof of principle for this interaction, conditioned medium from macrophages treated with palmitate (CM-PA) reduces insulin action and glucose uptake in muscle cells. However, the mechanism whereby CM-PA confers this negative response onto muscle cells remains unknown.

Methodology/Principal Findings

L6-GLUT4myc myoblasts were exposed for 24 h to palmitate-free conditioned medium from RAW 264.7 macrophages pre-treated with 0.5 mM palmitate for 6 h. This palmitate-free CM-PA, containing selective cytokines and chemokines, inhibited myoblast insulin-stimulated insulin receptor substrate 1 (IRS1) tyrosine phosphorylation, AS160 phosphorylation, GLUT4 translocation and glucose uptake. These effects were accompanied by a rise in c-Jun N-terminal kinase (JNK) activation, degradation of Inhibitor of κBα (IκBα), and elevated expression of proinflammatory cytokines in myoblasts. Notably, CM-PA caused IRS1 phosphorylation on Ser1101, and phosphorylation of novel PKCθ and ε. Co-incubation of myoblasts with CM-PA and the novel and conventional PKC inhibitor Gö6983 (but not with the conventional PKC inhibitor Gö6976) prevented PKCθ and ε activation, JNK phosphorylation, restored IκBα mass and reduced proinflammatory cytokine production. Gö6983 also restored insulin signalling and glucose uptake in myoblasts. Moreover, co-silencing both novel PKC θ and ε isoforms in myoblasts by RNA interference, but not their individual silencing, prevented the inflammatory response and restored insulin sensitivity to CM-PA-treated myoblasts.

Conclusions/Clinical Significance

The results suggest that the block in muscle insulin action caused by CM-PA is mediated by novel PKCθ and PKCε. This study re-establishes the participation of macrophages as a relay in the action of fatty acids on muscle cells, and further identifies PKCθ and PKCε as key elements in the inflammatory and insulin resistance responses of muscle cells to macrophage products. Furthermore, it portrays these PKC isoforms as potential targets for the treatment of fatty acid-induced, inflammation-linked insulin resistance.     

Life history and demography of Psyllaephagus zdeneki (Hymenoptera: Encyrtidae), a potential candidate for biological control of olive psylla,Euphyllura pakistanica (Hemiptera: Psyllidae)

Life history and demographic parameters of Psyllaephagus zdeneki Noyes and Fallahzadeh (Hymenoptera: Encyrtidae) were studied on its host the olive psyllid, Euphyllura pakistanica Loginova (Hemiptera: Psyllidae). Experiments were conducted in a growth chamber at 20±1 °C, relative humidity of 60±5%, and a photoperiod of 16:8 (L: D) hours. Four different olive cultivars (Fishomi, Shenge, Oil and Yellow) were used to test possible host plant influence on parasitoid performance. The pre-imaginal developmental period of female P. zdeneki varied from 24.96 (on Fishomi) to 26.34 (on Shenge) days, and for males from 21.63 (on Fishomi) to 24.44 (on Yellow) days. Adult female longevity differed significantly among the four cultivars, ranging from 12.46 (on Fishomi) to 14.97 (on Shenge) days. For each cultivar, adult female longevity was significantly greater than male longevity. Life table parameters showed survival rates (l _x ) in newly emerged females were 84.61, 82.25, 85.71 and 78.12% on Fishomi, Yellow, Shenge and Oil, respectively. Female egg deposition was highest on Yellow (138.4 eggs per female) and lowest on Fishomi (116.3 eggs per female). The highest and lowest intrinsic rate of increase were 0.28 (on Shenge) and 0.24 (on Oil), respectively. The mean generation time ranged from 14.6 (on Shenge) to 16.7 (on Oil) days. These results are discussed with respect to the potential impact P. zdeneki as a natural enemy of E. pakistanica, the most important pest of olive in the Fars province of Iran, as well as the influence of olive cultivar on parasitoid life table parameters.