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    IL-37 affects the occurrence and development of endometriosis by regulating the biological behavior of endometrial stromal cells through multiple signaling pathways.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, No. 138 tongzipo, Yuelu District, Changsha 100730,Hunan, China.
    Endometriosis (EMs) is a chronic inflammatory condition. Interleukin (IL)-37 is a member of the IL-1 family and an anti-inflammatory cytokine. This study aimed to evaluate the possible role of IL-37 in the EMs pathogenesis. Read More

    Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Komturstr. 3a, D-60528Frankfurt/Main, Germany.
    Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Read More

    Involvement of mitophagy in cisplatin-induced cell death regulation.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    MV Lomonosov Moscow State University, 119991Moscow, Russian Federation.
    Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. The removal of malfunctioning or damaged mitochondria is essential for normal cellular physiology and tissue development. Stimulation of mitochondrial permeabilization and release of proapoptotic factors from the intermembrane space is an essential step in triggering the mitochondrial pathway of cell death. Read More

    BNIP3 contributes to the glutamine-driven aggressive behavior of melanoma cells.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Cell Death Research & Therapy (CDRT) Laboratory, Department of Cellular and Molecular Medicine, O&N1 building from Campus Gasthuisberg, KU Leuven University of Leuven, Herenstraat 49, B-3000Leuven, Belgium.
    Aerobic glycolysis (Warburg effect) is used by cancer cells to fuel tumor growth. Interestingly, metastatic melanoma cells rely on glutaminolysis rather than aerobic glycolysis for their bioenergetic needs through the tricarboxylic acid cycle. Here, we compared the effects of glucose or glutamine on melanoma cell proliferation, migration and oxidative phosphorylation in vitro. Read More

    The role of acid sphingomyelinase and modulation of sphingolipid metabolism in bacterial infection.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Straße 2, D-97080Würzburg, Germany.
    Acid sphingomyelinase (ASM) is a key enzyme in sphingolipid metabolism that converts sphingomyelin to ceramide, thereby modulating membrane structures and signal transduction. Bacterial pathogens can manipulate ASM activity and function, and use host sphingolipids during multiple steps of their infection process. An increase in ceramides upon infection results in the formation of ceramide-enriched membrane platforms that serve to cluster receptor molecules and organize intracellular signaling molecules, thus facilitating bacterial uptake. Read More

    The two cathepsin B-like proteases of Arabidopsis thaliana are closely related enzymes with discrete endopeptidase and carboxydipeptidase activities.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Muthgasse 18, A-1190Vienna, Austria.
    The genome of the model plant Arabidopsis thaliana encodes three paralogues of the papainlike cysteine proteinase cathepsin B (AtCathB1, AtCathB2 and AtCathB3), whose individual functions are still largely unknown. Here we show that a mutated splice site causes severe truncations of the AtCathB1 polypeptide, rendering it catalytically incompetent. By contrast, AtCathB2 and AtCathB3 are effective proteases which display comparable hydrolytic properties and share most of their substrate specificities. Read More

    The function of sphingomyelinases in mycobacterial infections.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Molecular Biology, University of Duisburg-Essen, Hufelandstrasse 55, D-45122Essen, Germany.
    Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the deadliest and most important infectious diseases worldwide. The sphingomyelinase/ceramide system, which has been shown several times to be a crucial factor in the internalization, processing, and killing of diverse pathogens, also modulates the pro-inflammatory response and the state of mycobacteria in macrophages. Both acid and neutral sphingomyelinases are important in this activity. Read More

    Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052,Henan, China.
    The paxillin and M2 macrophage are all involved in cell proliferation and tumor progression, and this study aims to explore the interaction between them in colon cancer and the role of paxillin in cancer progression. Expression of mRNAs and proteins was determined by qRTPCR and western blot, separately. Endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Read More

    Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Inflammation Research Network-Snyder Institute for Chronic Disease, Departments of Physiology and Pharmacology and Medicine, University of Calgary Cumming School of Medicine, 3330 Hospital Drive NW,Calgary, AB, T2N 4N1,Canada.
    We propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinaseactivated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work shows that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes. Read More

    Interaction of volatile organic compounds and underlying liver disease: a new paradigm for risk.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Pharmacology and Toxicology, University of Louisville,Louisville, KY 40292,USA.
    Occupational and environmental exposures to industrial chemicals are known to cause hepatotoxicity and liver injury, in humans and in animal models. Historically, research has focused on severe acute liver injury (e.g. Read More

    Sphingolipid metabolism - an ambiguous regulator of autophagy in the brain.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    LIMES Institute, Unit Membrane Biology & Lipid Biochemistry, Kekulé-Institute of the University Bonn, Gerhard-Domagk-Str. 1, D-53121,Bonn, Germany.
    In mammals, the brain exhibits the highest lipid content in the body next to adipose tissue. Complex sphingolipids are characteristic compounds of neuronal membranes. Vital neural functions including information flux and transduction occur along these membranes. Read More

    Transglutaminase type 2 in the regulation of proteostasis.
    Biol Chem 2018 Jun 20. Epub 2018 Jun 20.
    Department of Biology, University of Rome 'Tor Vergata', Via della Ricerca Scientifica, I-00133 Rome, Italy.
    The maintenance of protein homeostasis (proteostasis) is a fundamental aspect of cell physiology that is essential for the survival of organisms under a variety of environmental and/or intracellular stress conditions. Acute and/or persistent stress exceeding the capacity of the intracellular homeostatic systems results in protein aggregation and/or damaged organelles that leads to pathological cellular states often resulting in cell death. These events are continuously suppressed by a complex macromolecular machinery that uses different intracellular pathways to maintain the proteome integrity in the various subcellular compartments ensuring a healthy cellular life span. Read More

    Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School at Houston,Houston, TX 77030,USA.
    Cellular protein homeostasis (proteostasis) is maintained by a broad network of proteins involved in synthesis, folding, triage, repair and degradation. Chief among these are molecular chaperones and their cofactors that act as powerful protein remodelers. The growing realization that many human pathologies are fundamentally diseases of protein misfolding (proteopathies) has generated interest in understanding how the proteostasis network impacts onset and progression of these diseases. Read More

    Modifications in small nuclear RNAs and their roles in spliceosome assembly and function.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, D-37073Göttingen, Germany.
    Modifications in cellular RNAs have emerged as key regulators of all aspects of gene expression, including pre-mRNA splicing. During spliceosome assembly and function, the small nuclear RNAs (snRNAs) form numerous dynamic RNA-RNA and RNA-protein interactions, which are required for spliceosome assembly, correct positioning of the spliceosome on substrate pre-mRNAs and catalysis. The human snRNAs contain several base methylations as well as a myriad of pseudouridines and 2'-O-methylated nucleotides, which are largely introduced by small Cajal body-specific-RNPs. Read More

    Cold atmospheric plasma treatment inhibits growth in colorectal cancer cells.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Institute of Biochemistry, University of Erlangen-Nuremberg, Fahrstrasse 17, D91054Erlangen, Germany.
    Plasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter - a device particularly developed for the treatment of tumor cells - that uses the Surface Micro Discharge (SMD) technology for plasma production in air. Read More

    Sphingolipids in inflammatory hypoxia.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany.
    Hypoxia due to rapid tumor growth with impaired neovascularization and inflammation resulting from immune cell activation are hallmarks of cancer. Hypoxia-inducible factors control transcriptional adaptation in response to low oxygen conditions, both in tumor and immune cells. In addition, sphingolipids become increasingly recognized as important cell mediators in tumor and inflammatory hypoxia. Read More

    Pathological manifestations of Farber disease in a new mouse model.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Department of Molecular Biology, University of Duisburg-Essen, Hufelandstraße 55, D- 45147Essen, Germany.
    Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of Farber Disease is still poorly understood. Read More

    Click reactions with functional sphingolipids.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    University of Würzburg, Institute of Organic Chemistry, Am Hubland, D-97074 Würzburg, Germany.
    Sphingolipids and glycosphingolipids can regulate cell recognition and signalling. Ceramide and sphingosine-1-phosphate are major players in the sphingolipid pathways and are involved in the initiation and regulation of signalling, apoptosis, stress responses and infection. Specific chemically synthesised sphingolipid derivatives containing small functionalities like azide or alkyne can mimic the biological properties of natural lipid species, which turns them into useful tools for the investigation of the highly complex sphingolipid metabolism by rapid and selective 'click chemistry' using sensitive tags like fluorophores. Read More

    CD4+ Foxp3+ regulatory T cell-mediated immunomodulation by anti-depressants inhibiting acid sphingomyelinase.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
    Acid sphingomyelinase (ASM) is the rate-limiting enzyme cleaving sphingomyelin into ceramide and phosphorylcholin. CD4+ Foxp3+ regulatory T (Treg) cells depend on CD28 signaling for their survival and function, a receptor that activates the ASM. Both, basal and CD28-induced ASM activities are higher in Treg cells than in conventional CD4+ T (Tconv) cells. Read More

    Upregulation of Twist is involved in Gli1 induced migration and invasion of hepatocarcinoma cells.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
    Hedgehog (Hh) signaling is involved in the progression of hepatocellular carcinoma (HCC), while its detailed mechanisms are not well illustrated. Our present study revealed that the expression of Gli1, while not Gli2 or Gli3, is significantly increased in HCC cell lines and 20/28 (71.4%) HCC tissues as compared with their corresponding controls. Read More

    New clues into the self-assembly of Vmh2, a basidiomycota class I hydrophobin.
    Biol Chem 2018 Jun 20. Epub 2018 Jun 20.
    Department of Chemical Sciences, University of Naples "Federico II", via Cintia 4, I-80126 Naples, Italy.
    Hydrophobins are fungal proteins that can self-assemble into amphiphilic films at hydrophobic-hydrophilic interfaces. Class I hydrophobin aggregates resemble amyloid fibrils, sharing some features with them. Here, five site-directed mutants of Vmh2, a member of basidiomycota class I hydrophobins, were designed and characterized to elucidate the molecular determinants playing a key role in class I hydrophobin self-assembly. Read More

    Model construction of Niemann-Pick type C disease in zebrafish.
    Biol Chem 2018 Jun 20. Epub 2018 Jun 20.
    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Donghu South Road 7#, Wuhan 430072, China.
    Niemann-Pick type C disease (NPC) is a rare human disease, with limited effective treatment options. Most cases of NPC disease are associated with inactivating mutations of the NPC1 gene. However, cellular and molecular mechanisms responsible for the NPC1 pathogenesis remain poorly defined. Read More

    Twitch or swim: towards the understanding of prokaryotic motion based on the type IV pilus blueprint.
    Biol Chem 2018 Jun;399(7):799-808
    Living Systems Institute, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
    Bacteria and archaea are evolutionarily distinct prokaryotes that diverged from a common ancestor billions of years ago. However, both bacteria and archaea assemble long, helical protein filaments on their surface through a machinery that is conserved at its core. In both domains of life, the filaments are required for a diverse array of important cellular processes including cell motility, adhesion, communication and biofilm formation. Read More

    Hypoxia and serum deprivation induces glycan alterations in triple negative breast cancer cells.
    Biol Chem 2018 Jun;399(7):661-672
    Biomarkers in Cancer Research Group (BmC) - Federal University of Pernambuco (UFPE), 50670-901 Recife, Pernambuco, Brazil.
    Triple negative breast cancer (TNBC) is a major global public health problem. The lack of targeted therapy and the elevated mortality evidence the need for better knowledge of the tumor biology. Hypoxia and aberrant glycosylation are associated with advanced stages of malignancy, tumor progression and treatment resistance. Read More

    Protein crystallization in living cells.
    Biol Chem 2018 Jun;399(7):751-772
    Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany.
    Protein crystallization in living cells has been observed surprisingly often as a native assembly process during the past decades, and emerging evidence indicates that this phenomenon is also accessible for recombinant proteins. But only recently the advent of high-brilliance synchrotron sources, X-ray free-electron lasers, and improved serial data collection strategies has allowed the use of these micrometer-sized crystals for structural biology. Thus, in cellulo crystallization could offer exciting new possibilities for proteins that do not crystallize applying conventional approaches. Read More

    DNA-encoded libraries - an efficient small molecule discovery technology for the biomedical sciences.
    Biol Chem 2018 Jun;399(7):691-710
    Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 6, D-44227 Dortmund, Germany.
    DNA-encoded compound libraries are a highly attractive technology for the discovery of small molecule protein ligands. These compound collections consist of small molecules covalently connected to individual DNA sequences carrying readable information about the compound structure. DNA-tagging allows for efficient synthesis, handling and interrogation of vast numbers of chemically synthesized, drug-like compounds. Read More

    Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3.
    Biol Chem 2018 Jun;399(7):649-659
    Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
    Colorectal cancer is the third most common cancer type worldwide. It is characterized by a high expression of aberrantly glycosylated ligands, such as the Tn antigen (GalNAcα1-Ser/Thr), which is a major ligand for the C-type lectin macrophage galactose-type lectin (MGL). We have previously determined that a high level of MGL ligands in colorectal tumors is associated with lower disease-free survival in patients with late stage disease, which we could attribute to the presence of oncogenic BRAFV600E mutations. Read More

    Spectroscopic characterization of the Co-substituted C-terminal domain of rubredoxin-2.
    Biol Chem 2018 Jun;399(7):787-798
    Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
    Pseudomonas putida rubredoxin-2 (Rxn2) is an essential member of the alkane hydroxylation pathway and transfers electrons from a reductase to the membrane-bound hydroxylase. The regioselective hydroxylation of linear alkanes is a challenging chemical transformation of great interest for the chemical industry. Herein, we report the preparation and spectroscopic characterization of cobalt-substituted P. Read More

    Regulation of LRRK2: insights from structural and biochemical analysis.
    Biol Chem 2018 Jun;399(7):637-642
    DZNE-German Center for Neurodegenerative Diseases, Otfried-Müller Str. 23, D-72076 Tübingen, Germany.
    Leucine-rich repeat kinase 2 (LRRK2) is a multi-domain protein and its mutations can lead to Parkinson's disease. Recent studies on LRRK2 and homologue proteins have advanced our mechanistic understanding of LRRK2 regulation. Here, we summarize the available data on the biochemistry and structure of LRRK2 and postulate three possible layers of regulation, translocation, monomer-dimer equilibrium and intramolecular activation of domains. Read More

    Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the ASCR, Prumyslova 595, 252 50 Vestec, Czech Republic.
    Kallikrein-related proteases (KLKs) play a critical role in epidermis physiology and have been implicated in skin pathologies such as Netherton syndrome. The contribution of individual KLKs to skin proteolysis is poorly understood. Monitoring of their activities in skin proteome is hampered by overlapping substrate specificities, and there is a need for novel assays. Read More

    Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Laboratory of Cellular Pathology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
    The kallikrein family comprises tissue kallikrein and 14 kallikrein-related peptidases (KLKs) recognized as a subgroup of secreted trypsin- or chymotrypsin-like serine proteases. KLKs are expressed in many cellular types where they regulate important physiological activities such as semen liquefaction, immune response, neural development, blood pressure, skin desquamation and tooth enamel formation. Tissue kallikrein, the oldest member and kinin-releasing enzyme, and KLK3/PSA, a tumor biomarker for prostate cancer are the most prominent components of the family. Read More

    Specificity profiling of human trypsin-isoenzymes.
    Biol Chem 2018 Jun 20. Epub 2018 Jun 20.
    Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FI-00290 Helsinki, Finland.
    In humans, three different trypsin-isoenzymes have been described. Of these, trypsin-3 appears to be functionally different from the others. In order to systematically study the specificity of the trypsin-isoenzymes, we utilized proteome-derived peptide libraries and quantitative proteomics. Read More

    Kallikrein-related peptidases and associated microRNAs as promising prognostic biomarkers in gastrointestinal malignancies.
    Biol Chem 2017 Dec 20. Epub 2017 Dec 20.
    Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis,AthensGR-15701,Greece.
    Gastrointestinal malignancies represent a wide spectrum of diseases of the gastrointestinal tract and its accessory digestive organs, including esophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. Malignancies of the gastrointestinal system are responsible for nearly 30% of cancer-related morbidity and approximately 40% of cancer-related mortality, worldwide. For this reason, the discovery of novel prognostic biomarkers that can efficiently provide a better prognosis, risk assessment, and prediction of treatment response is an imperative need. Read More

    Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    INSERM U1100, Centre d'Etude des Pathologies Respiratoires, Faculté de Médecine, F-37032 Tours, France.
    Every year, influenza A virus (IAV) affects and kills many people worldwide. The viral hemagglutinin (HA) is a critical actor in influenza virus infectivity which needs to be cleaved by host serine proteases to exert its activity. KLK5 has been identified as an activating protease in humans with a preference for the H3N2 IAV subtype. Read More

    Functional interrelationships between the kallikrein-related peptidases family and the classical kinin system in the human neutrophil.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Laboratory of Cellular Pathology, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, 5110712 Valdivia, Chile.
    In the human neutrophil, kallikrein-related peptidases (KLKs) have a significant functional relationship with the classical kinin system as a kinin B1 receptor agonist induces secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the medium. Secretion of KLK1, the kinin-forming enzyme, may perpetuate formation of kinin in the inflammatory milieu by hydrolyzing extravasated kininogens present in tissue edema. Secretion of KLKs into the inflammatory milieu, induced by kinins or other proinflammatory mediators, provides the human neutrophil with a wide range of molecular interactions to hydrolyze different cellular and extracellular matrix components, which may be of critical relevance in different mechanisms involving inflammation. Read More

    The forkhead domain hinge-loop plays a pivotal role in DNA binding and transcriptional activity of FOXP2.
    Biol Chem 2018 Jun 1. Epub 2018 Jun 1.
    Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, 1 Jan Smuts Ave, Braamfontein, 2050 Johannesburg,Gauteng, South Africa.
    FOX proteins are a ubiquitously expressed family of transcription factors that regulate development and differentiation of a wide range of tissues in animals. The FOXP subfamily members are the only known FOX proteins capable of forming domain-swapped forkhead domain dimers. This is proposed to be due to an evolutionary mutation (P539A) that lies in the forkhead domain hinge loop, a key region thought to fine-tune DNA sequence specificity in the FOX transcription factors. Read More

    Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, GR-15701 Athens, Greece.
    Tissue kallikrein, kallikrein-related peptidases (KLKs), and plasma kallikrein form the largest group of serine proteases in the human genome, sharing many structural and functional characteristics. In this study, we describe the molecular cloning of four novel splice variants of the human KLK11 and KLK12 genes, discovered by combining 3' rapid amplification of cDNA ends (3' RACE), next-generation sequencing (NGS) technology, advanced bioinformatic analysis and Sanger sequencing. Expression analysis of these new transcripts in cell lines originating from 17 cancerous and two normal tissues revealed the expression pattern of each transcript. Read More

    Novel approach to quorum quenching: rational design of antibacterials in combination with hexahistidine-tagged organophosphorus hydrolase.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Faculty of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia.
    N-acyl homoserine lactones (AHLs) are quorum sensing (QS) signal molecules used by most Gram-negative pathogenic bacteria. In this article the lactonase activity of the preparations based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) towards AHLs was studied. Initially, three of the most interesting β-lactam antibiotics were selected from seven that were trialed during molecular docking to His6-OPH. Read More

    Silencing of MED27 inhibits adrenal cortical carcinogenesis by targeting the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition process.
    Biol Chem 2018 May;399(6):593-602
    Department of Urology, Shanghai Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.
    This study aimed to explore the effect of MED27 on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortical carcinoma (ACC). The functional mechanism of MED27 on ACC processes was also explored. The expression of MED27 was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Read More

    Insulin-like signaling within and beyond metazoans.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Institute for Evolution and Biodiversity, University of Münster, Hüfferstrasse 1, D-48149 Münster, Germany.
    Insulin signaling is pivotal in controlling animals' lifespan and responses to environmental changes and, when altered, it may lead to pathogenic states. Despite its importance and relevance for biomedical research, insulin's mechanism of action and the full range of its pathophysiological effects remain incompletely understood. Likewise, the evolutionary origin of insulin and its associated signaling components are unclear. Read More

    Exploratory cell dynamics: a sense of touch for cells?
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, and Dortmund University of Technology, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Str. 4a, D-44227 Dortmund, Germany.
    Cells need to process multifaceted external cues to steer their dynamic behavior. To efficiently perform this task, cells implement several exploratory mechanisms to actively sample their environment. In particular, cells can use exploratory actin-based cell protrusions and contractions to engage and squeeze the environment and to actively probe its chemical and mechanical properties. Read More

    Oxidation of 1-N2-etheno-2'-deoxyguanosine by singlet molecular oxygen results in 2'-deoxyguanosine: a pathway to remove exocyclic DNA damage?
    Biol Chem 2018 May 31. Epub 2018 May 31.
    Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo (USP), Av. Prof. Lineu Prestes, 748, CEP 05508-000, Brazil.
    Exocyclic DNA adducts are considered as potential tools for the study of oxidative stress-related diseases, but an important aspect is their chemical reactivity towards oxidant species. We report here the oxidation of 1-N2-etheno-2'-deoxyguanosine (1,N2-εdGuo) by singlet molecular oxygen (1O2) generated by a non-ionic water-soluble endoperoxide [N,N'-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide (DHPNO2)] and its corresponding oxygen isotopically labeled [18O]-[N,N'-di(2,3-dihydroxypropyl)-1,4- naphthalenedipropanamide endoperoxide (DHPN18O2)], and by photosensitization with two different photosensitizers [methylene blue (MB) and Rose Bengal (RB)]. Products detection and characterization were achieved using high performance liquid chromatography (HPLC) coupled to ultraviolet and electrospray ionization (ESI) tandem mass spectrometry, and nuclear magnetic resonance (NMR) analyses. Read More

    Neuronal RNP granules: from physiological to pathological assemblies.
    Biol Chem 2018 Jun;399(7):623-635
    Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose, F-06100 Nice, France.
    Neuronal cells rely on macro- and micro-cellular compartmentalization to rapidly process information, and respond locally to external stimuli. Such a cellular organization is achieved via the assembly of neuronal ribonucleoprotein (RNP) granules, dynamic membrane-less organelles enriched in RNAs and associated regulatory proteins. In this review, we discuss how these high-order structures transport mRNAs to dendrites and axons, and how they contribute to the spatio-temporal regulation of localized mRNA translation. Read More

    Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism.
    Biol Chem 2018 May 1. Epub 2018 May 1.
    Sorbonne University, Faculty of Sciences and Engineering, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, F-75252 Paris, France.
    The activity of kallikrein-related peptidase 6 (KLK6) is deregulated in various diseases such as cancer and neurodegenerative diseases. KLK6 is thus considered as an attractive therapeutical target. In this short report, we depict some novel findings on the regulation of the KLK6 activity. Read More

    Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin.
    Biol Chem 2018 May 1. Epub 2018 May 1.
    Department of Molecular Biology, Medical School, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
    Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. Read More

    Silencing of MED27 inhibits adrenal cortical carcinogenesis by targeting the Wnt/β-catenin signaling pathway and the epithelial-mesenchymal transition process.
    Biol Chem 2017 Dec 20. Epub 2017 Dec 20.
    3Department of Urology, Shanghai Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.
    This study aimed to explore the effect of MED27 on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortex carcinoma (ACC). The functional mechanism of MED27 on ACC processes was also explored. The expression of MED27 was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Read More

    Hepatitis B virus X protein promotes proliferation of hepatocellular carcinoma cells by upregulating miR-181b by targeting ING5.
    Biol Chem 2018 May;399(6):611-619
    Infectious Disease Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, China.
    Hepatitis B virus X protein (HBx) played a key role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Emerging evidence has demonstrated that miR-181b and the inhibitor of growth protein 5 (ING5) participated in the pathophysiological process. However, the regulatory mechanism of HBx remained unknown. Read More

    From molecules to patients: exploring the therapeutic role of soluble guanylate cyclase stimulators.
    Biol Chem 2018 Jun;399(7):679-690
    Bayer AG, Drug-Discovery, Pharma Research Center Wuppertal, Aprather Weg 18a, D-42069 Wuppertal, Germany.
    Nitric oxide (NO) signaling represents one of the major regulatory pathways for cardiovascular function. After the discovery of NO, awarded with the Nobel Prize in 1998, this signaling cascade was stepwise clarified. We now have a good understanding of NO production and NO downstream targets such as the soluble guanylyl cyclases (sGCs) which catalyze cGMP production. Read More

    Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.
    Biol Chem 2018 Jun 19. Epub 2018 Jun 19.
    Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
    Kallikrein-related peptidase 6 (Klk6) is the most abundant serine proteinase in the adult central nervous system (CNS), yet we know little regarding its physiological roles or mechanisms of action. Levels of Klk6 in the extracellular environment are dynamically regulated in CNS injury and disease positioning this secreted enzyme to affect cell behavior by potential receptor dependent and independent mechanisms. Here we show that recombinant Klk6 evokes increases in intracellular Ca2+ in primary astrocyte monolayer cultures through activation of proteinase activated receptor 1 (PAR1). Read More

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