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https://www.readbyqxmd.com/read/28343356/development-of-a-novel-strategy-to-target-cd39-antithrombotic-activity-to-the-endothelial-platelet-microenvironment-in-kidney-ischemia-reperfusion-injury
#1
Maithili Sashindranath, Karen M Dwyer, Shala Dezfouli, Carly Selan, Sandra Crikis, Bo Lu, Yuping Yuan, Michael J Hickey, Karlheinz Peter, Simon C Robson, Peter J Cowan, Harshal H Nandurkar
Kidney ischemia-reperfusion injury (IRI) is common during transplantation. IRI is characterised by inflammation and thrombosis and associated with acute and chronic graft dysfunction. P-selectin and its ligand PSGL-1 are cell adhesion molecules that control leukocyte-endothelial and leukocyte-platelet interactions under inflammatory conditions. CD39 is the dominant vascular nucleotidase that facilitates adenosine generation via extracellular ATP/ADP-phosphohydrolysis. Adenosine signalling is protective in renal IRI, but CD39 catalytic activity is lost with exposure to oxidant stress...
March 25, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28343287/catabolic-effects-of-fgf-1-on-chondrocytes-and-its-possible-role-in-osteoarthritis
#2
Abdellatif El-Seoudi, Tarek Abd El Kader, Takashi Nishida, Takanori Eguchi, Eriko Aoyama, Masaharu Takigawa, Satoshi Kubota
Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model...
March 25, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28343225/clinical-trial-of-vadadustat-in-patients-with-anemia-secondary-to-stage-3-or-4-chronic-kidney-disease
#3
Edouard R Martin, Mark T Smith, Bradley J Maroni, Qing C Zuraw, Emil M deGoma
BACKGROUND: Therapeutic options for the treatment of anemia secondary to chronic kidney disease (CKD) remain limited. Vadadustat (AKB-6548) is an oral hypoxia-inducible factor prolyl-hydroxylase domain (HIF-PHD) inhibitor that is being investigated for the treatment of anemia secondary to CKD. METHODS: A phase 2a, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial (NCT01381094) was undertaken in adults with anemia secondary to CKD stage 3 or 4...
March 25, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28343163/s100a6-focus-on-recent-developments
#4
Wiesława Leśniak, Tomasz Wilanowski, Anna Filipek
The Ca2+-binding protein, S100A6, belongs to the S100 family. Binding of Ca2+ induces a conformational change, which causes an increase in the overall S100A6 hydrophobicity and allows it to interact with many targets. S100A6 is expressed in different normal tissues and in many tumors. Up to now it has been shown that S100A6 is involved in cell proliferation, cytoskeletal dynamics and tumorigenesis, and that it might have some extracellular functions. In this review, we summarize novel discoveries concerning S100A6 targets, its involvement in cellular signaling pathways, and presence in stem/progenitor cells, extracellular matrix and body fluids of diseased patients...
March 25, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28343162/mesothelin-promoter-variants-are-associated-with-increased-soluble-mesothelin-related-peptide-levels-in-asbestos-exposed-individuals
#5
Chiara De Santi, Perla Pucci, Alessandra Bonotti, Ombretta Melaiu, Monica Cipollini, Roberto Silvestri, Veronika Vymetalkova, Elisa Barone, Elisa Paolicchi, Alda Corrado, Irene Lepori, Irene Dell'Anno, Lucia Pellè, Pavel Vodicka, Luciano Mutti, Rudy Foddis, Alfonso Cristaudo, Federica Gemignani, Stefano Landi
BACKGROUND: Soluble mesothelin-related peptide (SMRP) is a promising diagnostic biomarker for malignant pleural mesothelioma (MPM), but various confounders hinder its usefulness in surveillance programmes. We previously showed that a single nucleotide polymorphism (SNP) within the 3'untranslated region (3'UTR) of the mesothelin (MSLN) gene could affect the levels of SMRP. OBJECTIVES: To focus on SNPs located within MSLN promoter as possible critical genetic variables in determining SMRP levels...
March 25, 2017: Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/28343145/effects-of-tiletamine-on-the-adenosine-monophosphate-activated-protein-kinase-signaling-pathway-in-the-rat-central-nervous-system
#6
Li-Xue Su, Xing-Xing Shi, Peng Yang, Hao Chen, Xin Li, Hong-Gang Fan, Hong-Bin Wang
OBJECTIVE: The dissociative anesthetic tiletamine, which acts on the central nervous system (CNS), is widely used in veterinary medicine and animal experiments. Recent studies indicate that adenosine 5'-monophosphate activated protein kinase (AMPK) plays a key role in the analgesic action of tiletamine. In the present study, the effects of tiletamine on the AMPK signaling pathway in rats were investigated. METHODS: Sprague-Dawley rats were injected intraperitoneally with tiletamine and executed at 10, 20, 40 and 60min post injection...
March 21, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28343137/synthesis-of-novel-muramic-acid-derivatives-and-their-interaction-with-lysozyme-action-of-lysozyme-revisited
#7
Manas Jana, Anirban Ghosh, Abhishek Santra, Rajiv Kumar Kar, Anup Kumar Misra, Anirban Bhunia
HYPOTHESIS: The interaction of lysozyme with the N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) unit of peptidoglycan (PGN) polymer of the bacterial cell wall is of immense importance to understand the mechanism of lysozyme on PGN. EXPERIMENTS: The synthesis of three novel NAM derivatives containing fused oxazinone ring to the NAM moiety has been achieved. The synthesized compounds were evaluated for their potential as a glycomimetic acceptor of lysozyme using different biophysical and computational methods such as (1)H NMR, STD NMR, DOSY and Molecular docking...
March 16, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#8
Tikam Chand Dakal, Rajender Kumar, Dindial Ramotar
Human organic cation transporters (hOCTs) belong to solute carriers (SLC) 22 family of membrane proteins that play a central role in transportation of chemotherapeutic drugs for several clinical and pathological conditions, including cancer and diabetes. These transporters mediate drug transport; however, the precise mechanism of drug-binding and transport by them is not fully uncovered yet, partly due to unavailability of any crystal structure record. In this work, we performed a multi-phasic approach to compute the 3D structural models of seven human organic cation transporters (hOCTs) starting from primary protein sequence...
March 18, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28343107/phosphorylated-tyrosine-based-pseudobioaffinity-adsorbent-for-the-purification-of-immunoglobulin-g
#9
Gisele Luiza Pavan, Igor Tadeu Lazzarotto Bresolin, Angélica Grespan, Sonia Maria Alves Bueno
The present study evaluated the phosphorylated-tyrosine (P-Tyr) based pseudobioaffinity adsorbent for the purification of human immunoglobulin G (IgG). P-Tyr was selected as a ligand to mimic the natural interactions that occur between the immunoreceptor tyrosine-based activation motif and the IgG. The ligand was coupled to bisoxirane-activated agarose gel and the effect of buffer system, pH, and conductivity was performed to elucidate the nature of IgG-P-Tyr interactions. P-Tyr-agarose was able to purify IgG from human plasma solution in HEPES buffer at pH 7...
March 21, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28343070/the-activation-of-akt-mtor-pathway-by-bleomycin-in-epithelial-to-mesenchymal-transition-of-human-submandibular-gland-cells-a-treatment-mechanism-of-bleomycin-for-mucoceles-of-the-salivary-glands
#10
Yu Cai, Rui Sun, Rong Wang, Jian-Gang Ren, Wei Zhang, Yi-Fang Zhao, Ji-Hong Zhao
OBJECTIVE: Bleomycin (BLM) has been found safe and highly effective in the treatment of the mucoceles by intralesional injection in our previous study. The present research was designed to investigate whether epithelial-to-mesenchymal transition (EMT) contributes to the therapeutic effects of BLM for mucoceles of the salivary glands. MATERIAL AND METHODS: The cell proliferation and apoptosis of human submandibular gland cells (HSG cells) were examined by Cell Counting Kit-8 assay and Annexin V binding assay respectively...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28343066/calcium-triggers-reversal-of-calmodulin-on-nested-anti-parallel-sites-in-the-iq-motif-of-the-neuronal-voltage-dependent-sodium-channel-nav1-2
#11
Liam Hovey, C Andrew Fowler, Ryan Mahling, Zesen Lin, Mark Stephen Miller, Dagan C Marx, Jesse B Yoder, Elaine H Kim, Kristin M Tefft, Brett C Waite, Michael D Feldkamp, Liping Yu, Madeline A Shea
Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel NaV1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca(2+))4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca(2+))4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1...
March 9, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28343052/season-of-treatment-initiation-with-antidepressants-and-suicidal-behavior-a-population-based-cohort-study-in-sweden
#12
Georgios D Makris, Johan Reutfors, Morten Andersen, Richard A White, Lisa Ekselius, Fotios C Papadopoulos
BACKGROUND: Decreased binding capacity of SERT in the prefrontal cortex has been observed in both suicide victims and suicide attempters. Moreover, some studies have shown that SERT has a seasonal variation with lower binding capacity in the spring and summer, which coincides with a seasonal peak of suicides. Our aim was to explore whether the season of treatment initiation with antidepressants is associated with suicide or suicide attempt and compare it with the underlying suicide seasonality in the general population...
March 10, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28343010/structural-and-dynamics-studies-of-the-tetr-family-protein-cprb-from-streptomyces-coelicolor-in-complex-with-its-biological-operator-sequence
#13
Hussain Bhukya, Asis K Jana, Neelanjana Sengupta, Ruchi Anand
In Streptomycetes, tetracycline repressor family of transcription regulators (TetR-FTRs) controls various biological processes including antibiotic biosynthesis, cellular morphology and innate resistance. Here, we focus on understanding the structural basis of transcription regulation by CprB, a member of TetR-FTRs from S. coelicolor. CprB is implicated as a receptor of γ-butyrolactones, a class of quorum sensing molecules, responsible for initiating secondary metabolic pathways. In order to understand the molecular mechanism of DNA recognition, the X-ray structure of CprB in complex with its biological relevant operator sequence was solved to a resolution of 3...
March 22, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28342983/lipid-quantification-by-raman-microspectroscopy-as-a-potential-biomarker-in-prostate-cancer
#14
Jordan O'Malley, Rahul Kumar, Andrey Kuzmin, Artem Pliss, Neelu Yadav, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Paras N Prasad, Dhyan Chandra
Metastatic castration recurrent prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28342965/effects-of-i2-imidazoline-receptor-ir-alkylating-bu99006-in-the-mouse-brain-upregulation-of-nischarin-i1-ir-and-%C3%AE-opioid-receptor-proteins-and-modulation-of-associated-signalling-pathways
#15
Benjamin Keller, Jesús A García-Sevilla
5-isothiocyanato-2-benzofuranyl-2-imidazoline (BU99006) was shown to selectively and irreversibly bind to I2-imidazoline receptors (IRs) in vitro and in vivo, but cell signalling consequences of I2-IR alkylation have not been reported previously. This study assessed by Western blot the effects of BU99006 on nischarin (candidate I1-IR), μ-OR (regulated by nischarin) and associated signalling mediators in the mouse brain. Acute treatment with BU99006 (20 mg/kg, i.p., 1-3 h) led to fast (peak at 1 h) and shortlasting (decline up to 3 h) upregulation of nischarin and μ-OR contents in the hippocampus (less or non-significant effects in cortex) and altered the expression of cytoskeletal β-actin (reduced contents at 3 h)...
March 23, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28342963/new-insights-into-cellular-cholesterol-acquisition-promoter-analysis-of-human-hmgcr-and-sqle-two-key-control-enzymes-in-cholesterol-synthesis
#16
Vicky Howe, Laura J Sharpe, Anika V Prabhu, Andrew J Brown
BACKGROUND: The two control points of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) are known targets of the transcription factor sterol-regulatory element binding protein-2 (SREBP-2). Yet the location of the sterol-regulatory elements (SREs) and cofactor binding sites, nuclear factor-Y (NF-Y) and specificity protein 1 (Sp1), have not been satisfactorily mapped in the human SQLE promoter, or at all in the human HMGCR promoter...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342939/recent-synthetic-and-medicinal-perspectives-of-dihydropyrimidinones-a-review
#17
REVIEW
Ramandeep Kaur, Sandeep Chaudhary, Kapil Kumar, Manish K Gupta, Ravindra K Rawal
Dihydropyrimidines are the most important heterocyclic ring systems which play an important role in the synthesis of DNA and RNA. Synthetically they were synthesized using Multi-component reactions like Biginelli reaction and Hantzschdihydropyridine. In the past decades, such Biginelli type dihydropyrimidones have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In this review, we highlight recent developments in this area, with a focus on the DHPMs, recently developed as anti-inflammatory, anti-HIV, anti-tubercular, antifungal anticancer, antibacterial, antifilarial, antihyperglycemic, antihypertensive, analgesic, anti-convulsant, antioxidant, anti-TRPA1, anti-SARS, and anti-cancer activity and α1a binding affinity...
March 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28342912/peanut-oleosins-associated-with-severe-peanut-allergy-importance-of-lipophilic-allergens-for-comprehensive-allergy-diagnostics
#18
Christian Schwager, Skadi Kull, Jochen Behrends, Niels Röckendorf, Frauke Schocker, Andreas Frey, Arne Homann, Wolf-Meinhard Becker, Uta Jappe
BACKGROUND: Peanut allergy is one of the most common and most severe food allergies in Western countries and its accurate diagnosis to prevent potential life-threatening allergic reactions is crucial. However, aqueous extracts used for routine diagnostic measurements are devoid of lipophilic allergens such as oleosins. We have recently succeeded in the isolation and purification of these unique proteins, and the current study evaluates their allergenic potential and clinical relevance...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28342889/heteromeric-complexes-of-aldo-keto-reductase-auxiliary-kv%C3%AE-subunits-akr6a-regulate-sarcolemmal-localization-of-kv1-5-in-coronary-arterial-myocytes
#19
Matthew A Nystoriak, Deqing Zhang, Ganapathy Jagatheesan, Aruni Bhatnagar
Redox-sensitive potassium channels consisting of the voltage-gated K(+) (KV) channel pore subunit KV1.5 regulate resting membrane potential and thereby contractility of vascular smooth muscle cells. Members of the KV1 family associate with cytosolic auxiliary β subunits, which are members of the aldo-keto reductase (AKR) superfamily (AKR6A subfamily). The Kvβ subunits have been proposed to regulate Kv1 gating via pyridine nucleotide cofactor binding. However, the molecular identity of KVβ subunits that associate with native KV1...
March 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28342876/increased-activity-of-unlinked-zika-virus-ns2b-ns3-protease-compared-to-linked-zika-virus-protease
#20
Benjamin D Kuiper, Kristin Slater, Nicholas Spellmon, Joshua Holcomb, Prasanna Medapureddy, Kendall M Muzzarelli, Zhe Yang, Reuben Ovadia, Franck Amblard, Iulia A Kovari, Raymond F Schinazi, Ladislau C Kovari
Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico...
March 22, 2017: Biochemical and Biophysical Research Communications
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