572 Biochemie
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Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration.
Lignins in general have been extensively studied, though the relation between source, isolation method and application is rarely described. In the present work, lignin from different sources (wheat straw and beech wood) and isolation methods (steam explosion, Organosolv) has been characterized regarding their application as a chemical resource and polymeric material. A range of analytical methods were applied including elemental analysis, FT-IR, 31P NMR, SEC, Py-GC-MS and HPLC to gain information about establish the purity, structure, molecular weight, thermal behavior and to determine carbohydrate residues according to the NREL protocol. TGA and DSC were used to study the thermal behavior of the isolated lignins and showed relatively low glass transition temperatures around 120 °C and decomposition temperatures between 340 and 380 °C. NREL analysis presented a carbohydrate-free lignin fraction derived from beech wood via Organosolv process which has not been achieved to date. The finding of this work supports Organolsolv as an efficient method to isolate pure lignin fractions from beech wood with practical value in industry, in particular for application in polyurethanes and phenolic resins.
Resistance to cell death often hampers anticancer therapies. Such resistance can arise during tumor development or during the treatment of cancer, when cells escape the natural or therapy-evoked cell death. They escape death by acquiring genetic or epigenetic alterations that disrupt the normal cell death pathways. These cell death pathways switch on a cell-intrinsic suicide program, termed apoptosis, whose key components are a family of proteases, the caspases. Caspase activity is controlled by activating or inhibiting proteins that are subject to regulation by two major pathways. The intrinsic pathway emanates from mitochondria and is regulated by proteins of the BCL-2 family. The extrinsic pathway is initiated by membrane-bound death receptors. Inhibitor of apoptosis proteins and heat shock proteins further modulate the execution of the apoptotic program. Knowledge about cancer-specific alterations of these pathways has paved the way for novel therapeutic approaches to overcome resistance to cell death.
In searching for new targets for antimalarials we investigated the biosynthesis of hypusine present in eukaryotic initiation factor-5A (eIF-5A) in Plasmodium. Here, we describe the cloning and expression of deoxyhypusine hydroxylase (DOHH), which completes the modi. cation of eIF-5A through hydroxylation of deoxyhypusine. The dohh cDNA sequence revealed an ORF of 1236 bp encoding a protein of 412 amino acids with a calculated molecular mass of 46.45 kDa and an isoelectric point of 4.96. Interestingly, DOHH from Plasmodium has a FASTA SCORE of only 27 compared with its human ortholog and contains several matches similar to E-Z-type HEAT-like repeat proteins (IPR004155 (InterPro), PF03130 (Pfam), SM00567 (SMART) present in the phycocyanin lyase subunits of cyanobacteria. Purified DOHH protein displayed hydroxylase activity in a novel in vitro DOHH assay, but phycocyanin lyase activity was absent. dohh is present as a single-copy gene and is transcribed in the asexual blood stages of the parasite. A signal peptide at the N-terminus might direct the protein to a different cellular compartment. During evolution, Plasmodium falciparum acquired an apicoplast that lost its photosynthetic function. It is possible that plasmodial DOHH arose from an E/F-type phycobilin lyase that gained a new role in hydroxylation.
