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Most cancers in youngsters as well as young people: analysis of vulnerability genetics inside 123 Italian sufferers.
The availability of metabolic intermediates is a prerequisite in many fields ranging from basic research, to biotechnological and biomedical applications as well as diagnostics. 2-keto-3-deoxy-6-phosphogluconate (KDPG) is the key intermediate of the Entner-Doudoroff (ED) pathway for sugar degradation and of sugar acid and sugar polymer breakdown in many organisms including human and plant pathogens. However, so far KDPG is hardly available due to missing efficient synthesis routes. We here report the efficient biocatalytic KDPG production through enzymatic dehydration of 6-phosphogluconate (6PG) up to gram scale using the 6PG dehydratase/Entner-Doudoroff dehydratase (EDD) from Caulobacter crescentus (CcEDD). The enzyme was recombinantly produced in Escherichia coli, purified to apparent homogeneity in a simple one-step procedure using nickel ion affinity chromatography, and characterized with respect to molecular and kinetic properties. The homodimeric CcEDD catalyzed the irreversible 6PG dehydration to KDPG with a V max of 61.6 U mg-1 and a K M of 0.3 mM for 6PG. Most importantly, the CcEDD showed sufficient long-term stability and activity to provide the enzyme in amounts and purity required for the efficient downstream synthesis of KDPG. CcEDD completely converted 1 g 6PG and a straight forward purification method yielded 0.81 g of stereochemically pure KDPG corresponding to a final yield of 90% as shown by HPLC-MS and NMR analyses. Copyright © 2020 Krevet, Shen, Bohnen, Schoenenberger, Meier, Obkircher, Bangert, Koehling, Allenspach, Siebers and Bräsen.Bacteriophage is a type of virus that could infect the host bacteria. They have been applied in the treatment of pathogenic bacterial infection. Phage enzymes and hydrolases play the most important role in the destruction of bacterial cells. Correctly identifying the hydrolases coded by phage is not only beneficial to their function study, but also conducive to antibacteria drug discovery. Thus, this work aims to recognize the enzymes and hydrolases in phage. A combination of different features was used to represent samples of phage and hydrolase. A feature selection technique called analysis of variance was developed to optimize features. The classification was performed by using support vector machine (SVM). The prediction process includes two steps. The first step is to identify phage enzymes. The second step is to determine whether a phage enzyme is hydrolase or not. The jackknife cross-validated results showed that our method could produce overall accuracies of 85.1 and 94.3%, respectively, for the two predictions, demonstrating that the proposed method is promising. Copyright © 2020 Li, Wang and Tang.There are many factors involved in wound healing, and the healing process is not static. The therapeutic effect of modern wound dressings in the clinical management of wounds is documented. However, there are few reports regarding the reasonable selection of dressings for certain types of wounds in the clinic. selleck inhibitor In this article, we retrospect the history of wound dressing development and the classification of modern wound dressings. In addition, the pros and cons of mainstream modern wound dressings for the healing of different wounds, such as diabetic foot ulcers, pressure ulcers, burns and scalds, and chronic leg ulcers, as well as the physiological mechanisms involved in wound healing are summarized. This article provides a clinical guideline for selecting suitable wound dressings according to the types of wounds. Copyright © 2020 Shi, Wang, Liu, Li, Li, Zhang, Liu, Shao and Wang.Ependymoma (EPN) is a rare primary tumor of the central nervous system (CNS) that affects both children and adults. Despite the definition and classification of distinct molecular subgroups, there remains a group of EPNs with a balanced genome, which makes it difficult to predict a prognosis of patients with EPN. The role of miRNA-mRNA network on EPN is still poorly understood. We assessed the involvement of miRNA-mRNA pairs in EPN by applying a weighted co-expression network analysis (WGCNA) approach. Using whole genome expression profile analysis followed by functional enrichment, we detected hub genes involved in active proliferation and DNA replication of nerve cells. Key genes including CYP11B1, KRT33B, RUNX1T1, SIK1, MAP3K4, MLANA, and SFRP5 identified in co-expression networks were regulated by miR-15a and miR-24-1. These seven miRNA-mRNA pairs were considered to influence not only pathways in cancer and tumor suppression process, but also MAPK, NF-kappaB, and WNT signaling pathways which were associated with tumorigenesis and development. This study provides a novel insight into potential diagnostic biomarkers of EPN and may have value in choosing therapeutic targets with clinical utility. Copyright © 2020 Liu, Dong, Mei and Huang.In the past 20 years, there have been several approaches to achieve cardioprotection or cardiac regeneration using a vast variety of cell therapies and remote ischemic pre-conditioning (RIPC). To date, substantial proof that either cell therapy or RIPC has the potential for clinically relevant cardiac repair or regeneration of cardiac tissue is still pending. Preclinical trials indicate that the secretome of cells in situ (during RIPC) as well as of transplanted cells may exhibit cardioprotective properties in the acute setting of cardiac injury. The secretome generally consists of cell-specific cytokines and extracellular vesicles (EVs) containing microRNAs (miRNAs). It is currently hypothesized that a subset of known miRNAs play a crucial part in the facilitation of cardioprotective effects. miRNAs are small non-coding RNA molecules that inhibit post-transcriptional translation of messenger RNAs (mRNAs) and play an important role in gene translation regulation. It is also known that one miRNAs usually targets multiple mRNAs. This makes predictability of pharmacokinetics and mechanism of action very difficult and could in part explain the inferior performance of various progenitor cells in clinical studies. Identification of miRNAs involved in cardioprotection and remodeling, the composition of miRNA profiles, and the exact mechanism of action are important to the design of future cell-based but also cell-free cardioprotective therapeutics. This review will give a description of miRNA with cardioprotective properties and a current overview on known mechanism of action and potential missing links. Additionally, we will give an outlook on the potential for clinical translation of miRNAs in the setting of myocardial infarction and heart failure. Copyright © 2020 Nazari-Shafti, Exarchos, Rodriguez Cetina Biefer, Cesarovic, Meyborg, Falk and Emmert.
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