50,104 results match your criteria increased affinity


Engineering a carbohydrate binding module to enhance chitinase catalytic efficiency on insoluble chitinous substrate.

Food Chem 2021 Mar 16;355:129462. Epub 2021 Mar 16.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address:

Development of a high-performance chitinase for efficient biotransformation of insoluble chitinous substrate would be highly valuable in industry. In this study, the chitin-binding domains (ChBDs) of chitinase SaChiA4 were successfully modified to improve the enzymatic activity. The engineered substitution variant R-SaChiA4, which had the exogenous ChBD of chitinase ChiA1 from Bacillus circulans WL-12 (ChBD) substituted for its original ChBD, increased its activity by nearly 54% (28. Read More

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An affinity prediction approach for the ligand of E3 ligase Cbl-b and an insight into substrate binding pattern.

Bioorg Med Chem 2021 Apr 2;38:116130. Epub 2021 Apr 2.

State Key Laboratory of Natural Medicines, and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Protein-protein interactions (PPIs) are essentially fundamental to all cellular processes, so that developing small molecule inhibitors of PPIs have great significance despite representing a huge challenge. Studying PPIs with the help of peptide motifs could obtain the structural information and reference significance to reduce the difficulty in the development of small molecules. Computational methods are powerful tools to characterize peptide-protein interactions, especially molecular dynamics simulation and binding free energy calculation. Read More

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Application of solid lipid nanoparticles as a long-term drug delivery platform for intramuscular and subcutaneous administration: in vitro and in vivo evaluation.

Eur J Pharm Biopharm 2021 Apr 10. Epub 2021 Apr 10.

University of Antwerp, Department of Pharmaceutical Technology and Biopharmacy, Universiteitsplein 1 2610 Wilrijk, Belgium, Kimberley. Electronic address:

The purpose of this work was to evaluate solid lipid nanoparticles (SLNs) as a long acting injectable drug delivery platform for intramuscular and subcutaneous administration. SLNs were developed with a low (unsaturated) and high (supersaturated) drug concentration at equivalent lipid doses. The impact of the drug loading as well as the administration route for the SLNs using two model compounds with different physicochemical properties were explored for their in vitro and in vivo performance. Read More

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A minigene DNA vaccine encoding peptide epitopes derived from Galectin-1 has protective antitumoral effects in a model of neuroblastoma.

Cancer Lett 2021 Apr 10. Epub 2021 Apr 10.

Pediatric Immunotherapy Group, Medical Faculty, Otto-von Guericke University of Magdeburg, Germany; Department of Environmental Immunology, Helmholtz Centre for Environmental Research -UFZ, Leipzig, Germany; Städtisches Klinikum Dessau, Academic Hospital of University Brandenburg, Dessau, Germany.

We recently identified Galectin-1 (Gal-1), a β-galactoside-binding lectin, as a novel immune regulator in neuroblastoma (NB). Here, we characterized the tolerogenic function of Gal-1 within the CD8 T cell compartment and further evaluated its relevance as an antigen for effective DNA vaccination against NB in a mouse model. NB cells with Gal-1 knockdown (NXS-2L) exhibited significantly reduced tumor growth compared to NXS-2 NB cells. Read More

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Neuroimaging Biomarkers of Chronic Traumatic Encephalopathy: Targets for the Academic Memory Disorders Clinic.

Neurotherapeutics 2021 Apr 13. Epub 2021 Apr 13.

Department of Neurology, Boston University Alzheimer's Disease Research Center, Boston University CTE Center, Boston University School of Medicine, 72 E Concord St, Suite B7800, MA, 02118, Boston, USA.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, such as those from contact sports. The pathognomonic lesion for CTE is the perivascular accumulation of hyper-phosphorylated tau in neurons and other cell process at the depths of sulci. CTE cannot be diagnosed during life at this time, limiting research on risk factors, mechanisms, epidemiology, and treatment. Read More

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An engineered ligand trap inhibits leukemia inhibitory factor as pancreatic cancer treatment strategy.

Commun Biol 2021 Apr 12;4(1):452. Epub 2021 Apr 12.

Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.

Leukemia inhibitory factor (LIF), a cytokine secreted by stromal myofibroblasts and tumor cells, has recently been highlighted to promote tumor progression in pancreatic and other cancers through KRAS-driven cell signaling. We engineered a high affinity soluble human LIF receptor (LIFR) decoy that sequesters human LIF and inhibits its signaling as a therapeutic strategy. This engineered 'ligand trap', fused to an antibody Fc-domain, has ~50-fold increased affinity (~20 pM) and improved LIF inhibition compared to wild-type LIFR-Fc, potently blocks LIF-mediated effects in pancreatic cancer cells, and slows the growth of pancreatic cancer xenograft tumors. Read More

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Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.

Commun Biol 2021 Apr 12;4(1):475. Epub 2021 Apr 12.

ModMab Therapeutics, Foster City, CA, USA.

COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10-15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. Read More

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Advances in Molecular Understanding of α-Helical Membrane-Active Peptides.

Acc Chem Res 2021 Apr 12. Epub 2021 Apr 12.

CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic.

ConspectusBiological membranes separate the interior of cells or cellular compartments from their outer environments. This barrier function of membranes can be disrupted by membrane-active peptides, some of which can spontaneously penetrate through the membranes or open leaky transmembrane pores. However, the origin of their activity/toxicity is not sufficiently understood for the development of more potent peptides. Read More

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Seagrass (Halophila stipulacea) invasion enhances carbon sequestration in the Mediterranean Sea.

Glob Chang Biol 2021 Apr 12. Epub 2021 Apr 12.

Global Change Research Group, IMEDEA (CSIC-UIB), Institut Mediterrani d'Estudis Avançats, Esporles, Spain.

The introduction and establishment of exotic species often result in significant changes in recipient communities and their associated ecosystem services. However, usually the magnitude and direction of the changes are difficult to quantify because there is no pre-introduction data. Specifically, little is known about the effect of marine exotic macrophytes on organic carbon sequestration and storage. Read More

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Soluble MD-2 and Heme in Sickle Cell Disease Plasma Promote Pro-Inflammatory Signaling in Endothelial Cells.

Front Immunol 2021 26;12:632709. Epub 2021 Mar 26.

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.

Recent evidence indicates that hemolysis in sickle cell disease (SCD) promotes inflammation innate immune signaling through toll-like receptor 4 (TLR4). Free heme released by hemolyzed red blood cells can bind to myeloid differentiation factor-2 (MD-2) and activate TLR4 pro-inflammatory signaling on endothelium to promote vaso-occlusion and acute chest syndrome in murine models of SCD. MD-2 is co-expressed with TLR4 on cell membranes, but in inflammatory conditions, soluble MD-2 (sMD-2) is elevated in plasma. Read More

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PB1 S524G mutation of wild bird-origin H3N8 influenza A virus enhances virulence and fitness for transmission in mammals.

Emerg Microbes Infect 2021 Apr 12:1-46. Epub 2021 Apr 12.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, 130122, China.

Influenza H3N8 viruses have been recovered frequently from wild bird species, including (primarily from migratory ducks) and (primarily from shorebirds). However, little attention has been given to the transmission ability of H3N8 avian influenza viruses among mammals. Here, we study the potential human health threat and the molecular basis of mammalian transmissibility of H3N8 avian influenza viruses isolated from wild bird reservoirs. Read More

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Congenital Erythrocytosis.

Eur J Haematol 2021 Apr 11. Epub 2021 Apr 11.

Department of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Erythrocytosis, or increased red cell mass, may be labelled as primary or secondary, depending on whether the molecular defect is intrinsic to the RBCs/their precursors or extrinsic to them, the latter being typically associated with elevated erythropoietin (EPO) levels. Inherited/congenital erythrocytosis (CE) of both primary and secondary types is increasingly recognized as the cause in many patients in whom acquired, especially neoplastic causes have been excluded. During the past two decades, the underlying molecular mechanisms of CE are increasingly getting unraveled. Read More

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Clinical Investigation on Endogenous Biomarkers to Predict Strong OAT-Mediated Drug-Drug Interactions.

Clin Pharmacokinet 2021 Apr 10. Epub 2021 Apr 10.

Drug Metabolism and Pharmacokinetics, Janssen Pharmaceutical Companies of Johnson & Johnson, Turnhoutseweg 30, 2340, Beerse, Belgium.

Background: Endogenous biomarkers are promising tools to assess transporter-mediated drug-drug interactions early in humans.

Methods: We evaluated on a common and validated in vitro system the selectivity of 4-pyridoxic acid (PDA), homovanillic acid (HVA), glycochenodeoxycholate-3-sulphate (GCDCA-S) and taurine towards different renal transporters, including multidrug resistance-associated protein, and assessed the in vivo biomarker sensitivity towards the strong organic anion transporter (OAT) inhibitor probenecid at 500 mg every 6 h to reach close to complete OAT inhibition.

Results: PDA and HVA were substrates of the OAT1/2/3, OAT4 (PDA only) and multidrug resistance-associated protein 4; GCDCA-S was more selective, having affinity only towards OAT3 and multidrug resistance-associated protein 2. Read More

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Cyclodextrin dimers: a versatile approach to optimizing encapsulation and their application to therapeutic extraction of toxic oxysterols.

Int J Pharm 2021 Apr 8:120522. Epub 2021 Apr 8.

Underdog Pharmaceuticals Inc., 110 Pioneer Way, Suite J; Mountain View, CA, USA 94041; SENS Research Foundation, 110 Pioneer Way, Suite J; Mountain View, CA, USA. Electronic address:

We have developed a novel class of specifically engineered, dimerized cyclodextrin nanostructures for the encapsulation of toxic biomolecules such as 7-ketocholesterol (7KC). 7KC accumulates over time and causes dysfunction in many cell types, linking it to several age-related diseases including atherosclerosis and age-related macular degeneration (AMD). Presently, treatments for these diseases are invasive, expensive, and show limited benefits. Read More

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Characterization and functional analysis of two acetylcholinesterase genes in Bradysia odoriphaga Yang et Zhang (Diptera: Sciaridae).

Pestic Biochem Physiol 2021 May 25;174:104807. Epub 2021 Feb 25.

Department of Entomology, China Agricultural University, Beijing 100193, China. Electronic address:

Two acetylcholinesterase genes (Boace1 and Boace2) were cloned from Bradysia odoriphaga, a devastating soil pest that mainly damages Chinese chives. The Boace1 encodes BoAChE1 protein consisting of 696 amino acid residues, while Boace2 encodes BoAChE2 containing 638 amino acids. Phylogenetic analysis showed that Boace1 and Boace2 are appeared to be distinct clusters. Read More

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Anti-GPR56 monoclonal antibody potentiates GPR56-mediated Src-Fak signaling to modulate cell adhesion.

J Biol Chem 2021 Jan 8;296:100261. Epub 2021 Jan 8.

The Brown Foundation Institute of Molecular Medicine and Center for Translational Cancer Research, University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address:

GPR56 is a member of the adhesion G-protein-coupled receptor family shown to play important roles in cell adhesion, brain development, immune function, and tumorigenesis. GPR56 is highly upregulated in colorectal cancer and correlates with poor prognosis. Several studies have shown GPR56 couples to the Gα class of heterotrimeric G-proteins to promote RhoA activation. Read More

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January 2021

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation.

J Clin Oncol 2021 Apr 9:JCO2003643. Epub 2021 Apr 9.

Anthony Nolan Research Institute, Royal Free Hospital, London, UK.

Purpose: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. Read More

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Therapeutic effect of oxyberberine on obese non-alcoholic fatty liver disease rats.

Phytomedicine 2021 Mar 17;85:153550. Epub 2021 Mar 17.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou 510120, PR China. Electronic address:

Background: Berberine (BBR) has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The metabolites of BBR were believed to contribute significantly to its pharmacological effects. Oxyberberine (OBB), a gut microbiota-mediated oxidative metabolite of BBR, has been firstly identified in our recent work. Read More

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Surface charged amino acid-based strategy for rational engineering of kinetic stability and specific activity of enzymes: Linking experiments with computational modeling.

Int J Biol Macromol 2021 Apr 5;182:228-236. Epub 2021 Apr 5.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China. Electronic address:

A rational workflow for engineering kinetically stable enzymes with good specific activity by surface charged amino acids engineering was proposed based on systematically analyzing the results of mutating 44 negatively charged surface amino acids of a thermophilic β-mannanase (ManAK). Computational data, combined with experimental results indicated that percentage side-chain solvent accessibility (PSSA), changes in Gibbs free energy of unfolding (∆∆G) and root-mean-square fluctuations (RMSF) could be suitable for screening kinetically stable mutants. A combinational standard (∆∆G < -0. Read More

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A dual surface inorganic molecularly imprinted BiWO-CuO/AgO heterostructure with enhanced activity-selectivity towards the photocatalytic degradation of target contaminantst.

Photochem Photobiol Sci 2020 Jul 27;19(7):943-955. Epub 2020 Oct 27.

Department of Gas and Petroleum, Yasouj University, 75918-74831, Gachsaran, Iran.

In this work, a high-surface-area dual inorganic molecularly imprinted (DIMI) BiWO/CuO/AgO photo-catalyst was developed for the selective photocatalytic degradation of methyl green (MG) and auramine O (AO) dyes as target pollutants. The DIMI-BiWO/CuO/AgO heterojunction was synthesized by a sono-chemically assisted sol-gel method by coating a layer of molecularly imprinted AgO/CuO on the surface of BiWO nanocubes with MG and AO as the templates. This was followed by calcination for the removal of target molecules and annealing for Ag/Cu oxide preparation. Read More

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Posaconazole micelles for ocular delivery: in vitro permeation, ocular irritation and antifungal activity studies.

Drug Deliv Transl Res 2021 Apr 8. Epub 2021 Apr 8.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.

Posaconazole (PSC) is a triazole group anti-fungal agent with the widest spectrum. Although there is no commercially available ocular dosage form, its diluted oral suspension preparation (Noxafil) is used as off-label in topical treatment of severe keratitis and sclerokeratitis in the clinic. However, ocular bioavailability of PSC suspension form is extremely low due to its highly lipophilic character. Read More

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A DNA Methylation Reader-Chaperone Regulator-Transcription Factor Complex Activates OsHKT1;5 Expression during Salinity Stress.

Plant Cell 2020 Nov;32(11):3535-3558

Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, Changchun 130024, People's Republic of China.

Irrigated lands are increasingly salinized, which adversely affects agricultural productivity. To respond to high sodium (Na+) concentrations, plants harbor multiple Na+ transport systems. Rice (Oryza sativa) HIGH-AFFINITY POTASSIUM (K+) TRANSPORTER1;5 (OsHKT1;5), a Na+-selective transporter, maintains K+/Na+ homeostasis under salt stress. Read More

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November 2020

Rational engraftment of quaternary-interactive acidic loops for anti-HIV-1 antibody improvement.

J Virol 2021 Apr 7. Epub 2021 Apr 7.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA

Broadly neutralizing antibodies (bNAbs) are the focus of increasing interest for human immunodeficiency virus type-1 (HIV-1) prevention and treatment. Although several bNAbs are already under clinical evaluation, the development of antibodies with even greater potency and breadth remains a priority. Recently, we reported a novel strategy for improving bNAbs against the CD4-binding site (CD4bs) of gp120 by engraftment of the elongated framework region 3 (FR3) from VRC03, which confers the ability to establish quaternary interactions with a second gp120 protomer. Read More

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Tonoplast-localized OsMOT1;2 participates in interorgan molybdate distribution in rice.

Plant Cell Physiol 2021 Apr 7. Epub 2021 Apr 7.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

Molybdenum (Mo) is an essential element for plant growth and is utilized by several key enzymes in biological redox processes. Rice assimilates molybdate ions via OsMOT1;1, a transporter with a high affinity for molybdate. However, other systems involved in the molecular transport of molybdate in rice remain unclear. Read More

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Design and identification of novel annomontine analogues against SARS-CoV-2: An approach.

Heliyon 2021 Apr 2;7(4):e06657. Epub 2021 Apr 2.

Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, 125, 201301, India.

Aims: COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31 December 2019 as "Pneumonia of unknown cause". Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. Read More

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Discovery of new pyrimidopyrrolizine/indolizine-based derivatives as P-glycoprotein inhibitors: Design, synthesis, cytotoxicity, and MDR reversal activities.

Eur J Med Chem 2021 Mar 27;218:113403. Epub 2021 Mar 27.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia; Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. Electronic address:

Targeting P-glycoprotein (P-gp, ABCB1 transporter), which plays an essential role in multi-drug resistance (MDR) in cancers, with new cytotoxic agents is a promising strategy in cancer chemotherapy. In the current study, we report the synthesis of thirteen novel pyrimidopyrrolizine, pyrimidoindolizine, and diazepinopyrrolizine derivatives. The new compounds exhibited cytotoxic activities against MCF7, A2780 and HT29 cancer cell lines (IC = 0. Read More

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