Discovery of Novel Antiangiogenic Marine Natural Product Scaffolds

Marine natural products (MNPs) are recognized for their structural complexity, diversity, and novelty. The vast majority of MNPs are pharmacologically relevant through their ability to modulate macromolecular targets underlying human diseases. Angiogenesis is a fundamental process in cancer progression and metastasis. Targeting angiogenesis through selective modulation of linked protein kinases is a valid strategy to discover novel effective tumor growth and metastasis inhibitors. An in-house marine natural products mini-library, which comprises diverse MNP entities, was submitted to the Lilly’s Open Innovation Drug Discovery platform. Accepted structures were subjected to in vitro screening to discover mechanistically novel angiogenesis inhibitors. Active hits were subjected to additional angiogenesis-targeted kinase profiling. Some natural and semisynthetic MNPs, including multiple members of the macrolide latrunculins, the macrocyclic oxaquinolizidine alkaloid araguspongine C, and the sesquiterpene quinone puupehenone, showed promising results in primary and secondary angiogenesis screening modules. These hits inhibited vascular endothelial growth factor (VEGF)-mediated endothelial tube-like formation, with minimal cytotoxicity at relevant doses. Secondary kinase profiling identified six target protein kinases, all involved in angiogenesis signaling pathways. Molecular modeling and docking experiments aided the understanding of molecular binding interactions, identification of pharmacophoric epitopes, and deriving structure-activity relationships of active hits. Marine natural products are prolific resources for the discovery of chemically and mechanistically unique selective antiangiogenic scaffolds.     

Calibration and Testing of the Aquacrop Model for Rice under Water and Nitrogen Management

The objective of this study was to adapt and test the ability of the AquaCrop model under different nitrogen and irrigation management conditions in northern Iran. A three-year field experiment was conducted at the experimental farm of the Iranian Rice Research Institute in Rasht, Iran, from 2005 to 2007. Irrigation treatments comprised continuous submergence, irrigation at 5-day intervals, and irrigation at 8-day intervals. Nitrogen (N) application levels were 0, 45, 60, and 75 kg N ha^?1. The goodness of fit between observed and simulated canopy cover, total and panicle biomass, grain yield, and final biomass was assessed by means of the coefficient of determination (R²) and the absolute and normalized root mean square errors (RMSE_n). Results of the statistical test of the model for total and panicle biomass showed moderately high R² (≥0.90) and moderate RMSE_n (6–36%) values, confirming that the model simulated the total and panicle biomass accurately. The model was simulated for CC with RMSE_n and R² of 28 and 0.82, respectively. The agreement between predicted and observed rice grain yield and final biomass were with R² of 0.81 and 0.82 and RMSE_n of 13 and 10% respectively.     

Chelate-enhanced phytoextraction and phytostabilization of lead-contaminated soils by carrot (Daucus carota)

The objective of this study was to study the influence of different ethylenediamine tetraacetate (EDTA), nitrilotriacetic acid (NTA) and oxalic acid (HOx) concentrations on tolerance and lead (Pb) accumulation capacity of carrot (Daucus carota). The results indicated that by increasing Pb, NTA and HOx concentrations in the soil, the shoot, taproot and capillary root dry matters increase effectively. In contrary, EDTA caused to reduce capillary roots biomass. EDTA was more effective than NTA and HOx in solubilizing soil Pb. The highest Pb content in shoots (342.2 ± 13.9 mg kg^?1) and taproots (301 ± 15.5 mg kg^?1) occurred in 10 mM EDTA, while it occurred for capillary roots (1620 ± 24.6 mg kg^?1) in 5 mM HOx, when the soil Pb concentration was 800 mg kg^?1. The obtained high phytoextraction and phytostabilization potentials were 1208 (±25.6) and 11.75 (±0.32) g Pb ha^?1 yr^?1 in 10 mmol EDTA kg^?1 soil and no chelate treatments, respectively. It may be concluded that chelate application increases Pb uptake by carrots. Consequently, this plant can be introduced as a hyperaccumulator to phytoextract and phytostabilize Pb from contaminated soils.     

伊朗南部Hara生物圈保护区内两种鸟类羽毛中镍含量比较(英文)

2010年11–12月,我们在伊朗南部Hara生物圈保护区调查并分析了黄喉岩鹭(Egretta gularis)和灰林银鸥(Larus heuglini)羽毛中的镍含量。根据方差分析,同一鸟种羽毛中镍含量在不同性别和年龄组之间均无显著差异,但这一结果的有效性受到本研究样本较小的影响。Student t检测结果表明灰林银鸥羽毛中镍含量高于黄喉岩鹭。雌性黄喉岩鹭羽毛中镍含量高于雄性,而雄性灰林银鸥羽毛中镍含量则高于雌性。     

Preparation and characterization of Ceftazidime loaded electrospun silk fibroin/gelatin mat for wound dressing

Fabrication of Ceftazidime (CTZ) loaded silk fibroin/gelatin (SF/GT) nanofibers (NFs) without the loss of structure and bioactivity of CTZ was demonstrated by electrospinning method. The structure, morphology and mechanical properties of the electrospun SF/GT nanofibrous mats were characterized using FT-IR, SEM and DSC. The drug release profile of different electrospun fibers was analyzed using spectrophotometric method, and also diffusion method was applied to assess the antibacterial effect of NFs. Cell viability was evaluated by MTT assay. The results show that the average diameter of drug loaded NFs at the optimum polymer to drug feeding ratio (10:1) was 276.55±35.8 nm, while increasing the feeding ratio to 1:1 increases the average diameter to 825.02±70.3 nm. FT-IR of drug loaded NFs was revealed that CTZ was successfully encapsulated into NFs while viability study approved cytocompatibility of SF/GT NFs. CTZ was released from NFs during 6 h, and formation of inhibition zone in diffusion test demonstrated the antibacterial effect of drug loaded NFs. Altogether, the CTZ loaded SF/GT NFs can improve the drug effectiveness particularly in the prevention of post-surgical adhesions and infections for wound dressing.     

No detected hepatitis B virus-DNA in thalassemic patients infected by hepatitis C virus in Kerman province of Iran

This research was aimed to investigate the prevalence and clinical impact of occult HBV infection in thalassemic patients with chronic HCV infection. In this cross-sectional study we have totally examined 60 patients suffering HBV and HCV infections by PCR and RT-PCR methods, respectively, in Kerman province of Iran. ELISA technique (RADIM, Italy) was used to detect anti-HBc, anti-HBs and HBsAg. The serum level of liver enzymes (SGOT, SGPT, DB, TB and ALK) were analyzed in the HCV infected patients (MAN, IRAN). Statistical analyses performed using t-test and Chi-square. We found that 27 cases (out of 60) were infected by HCV but HBV-DNA was not seen in HCV infected patients. Present findings also showed that none of samples were HBsAg positive but 9 (33%) (out of 27) HCV-RNA positive patients were anti-HBc positive and 11 (40.7%) were positive for anti-HBs. We found that SGOT, SGPT, DB, TB and ALK are above normal in 27 (100%), 19(70.3%), 12(44.5%), 15 (55.5%) and 15 (55.5%) RNA-HCV positive patients, respectively. The prevalence of hepatitis C infection is very high in thalassemic patients and based on other studies our results showed that the prevalence of HCV infection in Kerman is more than other provinces of Iran. In contrast with other studies HBV-DNA in these patients could not be detected, hence, it seems that occult HBV infection isn't frequent in Iranian thalassemic patients who suffering from chronic HCV infection.     

Siberian sturgeon (Acipenser baerii) larvae fed Artemia nauplii enriched with poly‐β‐hydroxybutyrate (PHB): effect on growth performance,body composition,digestive enzymes,gut microbial community,gut histology and stress tests

The effects of feeding Artemia nauplii enriched with or without poly‐β‐hydroxybutyrate (PHB) and/or highly unsaturated fatty acids (HUFA) on Siberian sturgeon (Acipenser baerii) larvae were investigated. Feeding larvae with PHB‐enriched nauplii (PHB, PHB + HUFA) decreased the growth performance of the larvae. PHB affected the body composition by increasing the lipid content of the whole body and decreasing total saturated, monoenoic, n3, n6 and decosahexanoeic acid (DHA) in the larvae, indicating that the PHB addition affected lipid metabolism. A high activity of pepsin was observed in the digestive extracts of PHB treatments (PHB, PHB + HUFA), while PHB suppressed amylase activity in the intestine of the larvae. Based on molecular analysis, PHB changed the microbial community in the distal intestine of the larvae. The highest counts of goblet cells were observed in the HUFA‐containing treatments (HUFA, PHB + HUFA), indicating that HUFA addition may improve the mucosal barrier defence system. The overall quality of the larvae was evaluated by exposing them to different salinities and ammonia stress levels. PHB decreased survival rates in these challenges. Our results show that optimal PHB doses for bio‐encapsulation into Artemia remain to be determined for further application at the earliest larval stages of sturgeon.     

Higher grain yield and higher grain protein deviation underline the potential of hybrid wheat for a sustainable agriculture

Grain yield and protein content are traits of major importance in wheat breeding, but their combination is challenging due to a tight negative correlation. Protein yield and grain protein deviation have been proposed as selection criteria to simultaneously improve both traits. Sedimentation volume is an indicator of protein quality, which plays an important role for bread‐making quality in wheat. All these traits have been investigated in our study with 135 parental inbred lines, their 1,604 hybrids and 10 commercial check varieties evaluated at five environments. The focus of our study was to investigate the usefulness of the grain protein deviation and to define a bivariate model for calculating the grain protein deviation. Further, we compared line and hybrid wheat for grain yield and quality‐related parameters such as protein content and sedimentation volume. The grain protein deviation determined with a bivariate model delivered robust estimates of variance components and enabled a balanced selection of genotypes with improved protein content and grain yield across different quality classes. Although heterosis for protein content and sedimentation volume was negative, hybrids had a higher grain protein deviation as well as higher grain yield at a given sedimentation volume or a given protein content than line varieties.     

Standardization of the outbred BALB/c mice as a suitable animal model for <Emphasis Type="BoldItalic">Besnoitia caprae</Emphasis> studies

The Apicomplexan parasite Besnoitia caprae infects wild and domestic goats. Knowledge on Besnoitia caprae specially an optimized animal model is sparse. Experimental infections with tachyzoites of BC-Pars obtained from BALB/c mice were conducted in outbred mice to determine the infectivity and LD50 of Besnoitia caprae. Six groups of five mice were intraperitoneally infected with 12.5 × 10³, 25 × 10³, 5 × 10⁴, 1 × 10⁵ and 2 × 10⁵ tachyzoites and a control inoculum of DMEM, respectively. Although morbidity and mortality were observed in all groups, two mice in the 12.5 × 10³ group showed alopecia and skin lesions on 60 days post-infection (DPI). Histopathological and molecular examination of skins confirmed B. caprae infection. The LD₅₀ was calculated as 25 × 10^3.2 tachyzoites per mouse. The results indicate that outbred BALB/c mice can be used as a suitable model of besnoitiosis and to screen candidate treatments and to test the efficacy of vaccines for besnoitiosis.     

Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma

Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine osteosarcomas, whereas cat samples more often displayed moderate levels. High levels of pro-MMP9, pro-MMP2, and active MMP2 were detected by gelatin zymography in both species, with significantly higher values for active MMP2 in canine osteosarcoma. These findings indicate that MMP2 is probably involved in canine and feline osteosarcoma and their expression and activity could be associated with the different metastatic behavior of canine and feline osteosarcoma.