Inhibition of alpha-glucosidase by aqueous extracts of some potent antidiabetic medicinal herbs

Diabetes mellitus is one of the most prevalant diseases of adults. Agents with alpha-glucosidase inhibitory activity have been useful as oral hypoglycemic drugs for the control of hyperglycemia in patients with type 2; noninsulin-dependent, diabetes mellitus (NIDDM). Investigation of some medicinal herbs: Urtica dioica, Taraxacum officinale, Viscum album, and Myrtus communis with alpha-glucosidase inhibitor activity was conducted to identify a prophylactic effect for diabetes in vitro. All plants showed differing potent alpha-glucosidase inhibitory activity. However, Myrtus communis strongly inhibited the enzyme (IC50 = 38 microg/mL). The inhibitory effect of these plants and some common antidiabetic drugs against the enzyme source (baker's yeast, rabbit liver, and small intestine) were also searched. Approximately all inhibitors used in this study showed quite different inhibitory activities, according to alpha-glucosidase origins. Furthermore, subsequent separation of the active material from Myrtus communis by HPLC showed that only one fraction acted as an a-glucosidase inhibitor.     

Cell-specific targeting of nanoparticles by multivalent attachment of small molecules

Nanomaterials with precise biological functions have considerable potential for use in biomedical applications. Here we investigate whether multivalent attachment of small molecules can increase specific binding affinity and reveal new biological properties of such nanomaterials. We describe the parallel synthesis of a library comprising 146 nanoparticles decorated with different synthetic small molecules. Using fluorescent magnetic nanoparticles, we rapidly screened the library against different cell lines and discovered a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. Hits from the last-mentioned screen were shown to target pancreatic cancer in vivo. The method and described materials could facilitate development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types.     

Molecular dynamics,thermodynamic, and mutational binding studies for tumor-specific LyP-1 in complex with p32

Recent studies in tumor homing peptides have shown the specificity of LyP-1 (CGNKRTRGC) to tumor lymphatics. In this present work, we evaluated the possible interactions between cyclic LyP-1 and its receptor, p32, with molecular dynamics and docking studies in order to lead the design of novel LyP-1 derivatives, which could bind to p32 more effectively and perform enhanced antitumor effect. The total binding enthalpy energies have been obtained by MM-PBSA thermodynamic computations and the favorability of p32.LyP-1 complex in water has been shown by explicit water MD computations. The last 30 ns of molecular dynamics trajectory have shown the strong interaction of LyP-1 with the inner surface chains of p32, especially with chains B and C. ALA-SCAN mutagenesis studies have indicated the considerable influence of Asn3, Lys4, Arg5, and Arg7 amino acid residues on the specific binding of LyP-1. Within the knowledge of the critical role of p32 receptor in cancer cell metabolism, this study can lead to further developments in anticancer therapy by targeting p32 with LyP-1 derivatives as active targeting moiety. This data can also be applied for the development of new drug delivery systems in which LyP-1 can be used for its targeting and anticancer properties.     

PepBank - a database of peptides based on sequence text mining and public peptide data sources

Background  

Peptides are important molecules with diverse biological functions and biomedical uses. To date, there does not exist a single, searchable archive for peptide sequences or associated biological data. Rather, peptide sequences still have to be mined from abstracts and full-length articles, and/or obtained from the fragmented public sources.     

Early exposure to IL-4 stabilizes IL-4 mRNA in CD4+ T cells via RNA-binding protein HuR

The mechanisms regulating IL-4 mRNA stability in differentiated T cells are not known. We found that early exposure of CD4+ T cells to endogenous IL-4 increased IL-4 mRNA stability. This effect of IL-4 was mediated by the RNA-binding protein HuR. IL-4 mRNA interacted with HuR and the dominant binding site was shown within the coding region of IL-4 mRNA. Exposure of CD4+ T cells to IL-4 had no effects on HuR expression or subcellular localization, but triggered HuR binding to IL-4 mRNA. Thus, IL-4 plays a positive role in maintaining IL-4 mRNA stability in CD4+ T cells via a HuR-mediated mechanism.     

The comparison of three methods for chromosomal abnormality detection

The connection between certain human diseases and abnormal changes in chromosomes was discovered nearly 50 years ago. However, the detection of these abnormalities turned out to be a difficult task because both microscopic technologies and biochemical diagnostic techniques have their limitations. In the beginning of the century, a method for multiple comparative genome hybridization (array CGH) was introduced and is now been widely used in clinical practice for biochemical diagnostics. The application of array CGH greatly reduces the statistical errors, but not the noise in the results. As such, the time and material expenses necessary for reliable localization of abnormal parts of chromosomes by the means of biochemical techniques, is not significantly reduced. Algorithms for localization of contrast parts in noisy sequences can improve the situation. We implemented and tested two algorithms for this purpose. The first is the "edge detector" algorithm introduced by J. Canny. The second one is the DotHelix algorithm developed by A. M. Leontovich, L. I. Brodsky, and A. E. Gorbalenya. In this paper we compare the two implementations against biochemical method in processing data produced by array CGH.     

Biological ancestries, kinship connections, and projected identities in four central Anatolian settlements: insights from culturally contextualized genetic anthropology

Previous population genetics studies in Turkey failed to delineate recent historical and social factors that shaped Anatolian cultural and genetic diversity at the local level. To address this shortcoming, we conducted focused ethnohistorical fieldwork and screened biological samples collected from the Yuksekyer region for mitochondrial, Y chromosome, and autosomal markers and then analyzed the data within an ethnohistorical context. Our results revealed that, at the village level, paternal genetic diversity is structured among settlements, whereas maternal genetic diversity is distributed more homogenously, reflecting the strong patrilineal cultural traditions that transcend larger ethnic and religious structures. Local ancestries and origin myths, rather than ethnic or religious affiliations, delineate the social boundaries and projected identities among the villages. Therefore, we conclude that broad, ethnicity-based sampling is inadequate to capture the genetic signatures of recent social and historical dynamics, which have had a profound influence on contemporary genetic and cultural regional diversity.