96,240 results match your criteria affinity receptor

12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) induces cell growth and improves barrier function through BLT2 interaction in intestinal epithelial Caco-2 cell cultures.

Biochem Pharmacol 2021 Jun 20:114663. Epub 2021 Jun 20.

epartment of Nutrition, Food Sciences and Gastronomy, Institute of Nutrition and Food Safety, University of Barcelona, Campus Torribera, Barcelona, Spain; CIBEROBN Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an unusual product of the cyclooxygenase pathway that is an endogenous ligand of the low-affinity receptor for leukotriene 4 (LTB), BLT2. Recent findings suggested that BLT2 possibly plays an important role in the healing of intestinal lesions and the regulation of barrier function. Here, we studied the role of 12-HHT on intestinal epithelial cell growth and the paracellular permeability of intestinal epithelium using Caco-2 cell cultures as experimental model. Read More

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Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells.

Cell Rep 2021 Jun;35(12):109286

Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. Electronic address:

B cell responses are critical for antiviral immunity. However, a comprehensive picture of antigen-specific B cell differentiation, clonal proliferation, and dynamics in different organs after infection is lacking. Here, by combining single-cell RNA and B cell receptor (BCR) sequencing of antigen-specific cells in lymph nodes, spleen, and lungs after influenza infection in mice, we identify several germinal center (GC) B cell subpopulations and organ-specific differences that persist over the course of the response. Read More

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Diversity-Oriented A-Macrocyclization for Studying Influences of Ring-Size and Shape of Cyclic Peptides: CD36 Receptor Modulators.

J Med Chem 2021 Jun 23. Epub 2021 Jun 23.

Département de Chimie, Université de Montréal, C.P. 6128, Succursale, Centre-Ville, Montréal, Québec H3C 3J7, Canada.

Cyclic peptide diversity has been broadened by elaborating the A-macrocyclization to include various di-amino carboxylate components with different -amine substituents. Triple-bond reduction provided new cyclic peptide macrocycles with -olefin and completely saturated structures. Moreover, cyclic azasulfurylpeptides were prepared by exchanging the propargylglycine (Pra) component for an amino sulfamide surrogate. Read More

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Allosteric Cross-Talk among Spike's Receptor-Binding Domain Mutations of the SARS-CoV-2 South African Variant Triggers an Effective Hijacking of Human Cell Receptor.

J Phys Chem Lett 2021 Jun 23:5987-5993. Epub 2021 Jun 23.

CNR-IOM c/o SISSA, via Bonomea 265, 34136 Trieste, Italy.

The rapid and relentless emergence of novel highly transmissible SARS-CoV-2 variants, possibly decreasing vaccine efficacy, currently represents a formidable medical and societal challenge. These variants frequently hold mutations on the Spike protein's receptor-binding domain (RBD), which, binding to the angiotensin-converting enzyme 2 (ACE2) receptor, mediates viral entry into host cells. Here, all-atom molecular dynamics simulations and dynamical network theory of the wild-type and mutant RBD/ACE2 adducts disclose that while the N501Y mutation (UK variant) enhances the Spike's binding affinity toward ACE2, the concomitant N501Y, E484K, and K417N mutations (South African variant) aptly adapt to increase SARS-CoV-2 propagation via a two-pronged strategy: (i) effectively grasping ACE2 through an allosteric signaling between pivotal RBD structural elements and (ii) impairing the binding of antibodies elicited by infected or vaccinated patients. Read More

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On-Cell NMR Contributions to Membrane Receptor Binding Characterization.

Chempluschem 2021 Jun 7;86(6):938-945. Epub 2021 Jun 7.

Department of Structural and Computational Biology, Max Perutz Laboratories, University of Vienna, Vienna Biocenter Campus 5, 1030, Vienna, Austria.

NMR spectroscopy has matured into a powerful tool to characterize interactions between biological molecules at atomic resolution, most importantly even under near to native (physiological) conditions. The field of in-cell NMR aims to study proteins and nucleic acids inside living cells. However, cells interrogate their environment and are continuously modulated by external stimuli. Read More

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Consensus clustering of single-cell RNA-seq data by enhancing network affinity.

Brief Bioinform 2021 Jun 23. Epub 2021 Jun 23.

Department of Molecular and Cellular Biosciences at Rowan University, Rowan University, NJ 08028, USA.

Elucidation of cell subpopulations at high resolution is a key and challenging goal of single-cell ribonucleic acid (RNA) sequencing (scRNA-seq) data analysis. Although unsupervised clustering methods have been proposed for de novo identification of cell populations, their performance and robustness suffer from the high variability, low capture efficiency and high dropout rates which are characteristic of scRNA-seq experiments. Here, we present a novel unsupervised method for Single-cell Clustering by Enhancing Network Affinity (SCENA), which mainly employed three strategies: selecting multiple gene sets, enhancing local affinity among cells and clustering of consensus matrices. Read More

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Main interactions of dopamine and risperidone with the dopamine D2 receptor.

Phys Chem Chem Phys 2021 Jun 23. Epub 2021 Jun 23.

Departamento de Química, División de Ciencias Básicas e Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa. AP Postal 55-534, CP 09340, CDMX, Mexico.

Psychosis is one of the psychiatric disorders that is controlled by dopaminergic drugs such as antipsychotics that have affinity for the dopamine D2 receptor (DRD2). In this investigation we perform quantum chemical calculations of two molecules [dopamine and risperidone] within a large cavity of DRD2 that represents the binding site of the receptor. Dopamine is an endogenous neurotransmitter and risperidone is a second-generation antipsychotic. Read More

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Computational Lock and Key and Dynamic Trajectory Analysis of Natural Biophors Against COVID-19 Spike Protein to Identify Effective Lead Molecules.

Mol Biotechnol 2021 Jun 22. Epub 2021 Jun 22.

Department of Chemical and Environmental Engineering, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, 43500, Semenyih, Selangor Darul Ehsan, Malaysia.

New pandemic infection of coronaviridae family virus spread to more than 210 countries with total infection of 1,136,851 and 62,955 (4.6%) deaths until 5th April 2020. Which stopped the regular cycle of humankind but the nature is consistently running. Read More

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Protocol to extract actively translated mRNAs from mouse hypothalamus by translating ribosome affinity purification.

STAR Protoc 2021 Jun 9;2(2):100589. Epub 2021 Jun 9.

Department of Molecular & integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.

Here, we present an in-depth protocol for extracting ribosome-bound mRNAs in low-abundance cells of hypothalamic nuclei. mRNAs are extracted from the micropunched tissue using refined translating ribosome affinity purification. Isolated RNAs can be used for sequencing or transcript quantification. Read More

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Molecular docking studies of α-mangostin, γ-mangostin, and xanthone on peroxisome proliferator-activated receptor gamma diphenyl peptidase-4 enzyme, and aldose reductase enzyme as an antidiabetic drug candidate.

J Adv Pharm Technol Res 2021 Apr-Jun;12(2):196-208. Epub 2021 Apr 27.

Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Institute Technology Bandung, Bandung, West Java.

α-mangostin, γ-mangostin, and xanthone are some of the marker compounds found in mangosteen ( Linn.) whose activity on several treatment targets including toward the peroxisome proliferator-activated receptor gamma (PPAR-γ) receptors, diphenyl peptidase 4 (DPP-4) enzyme, and aldose reductase enzyme is unknown. Although this plant has been predicted to be used as an alternative antidiabetic treatment, it has been proven through several previous studies. Read More

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IRDye800CW labeled uPAR-targeting peptide for fluorescence-guided glioblastoma surgery: Preclinical studies in orthotopic xenografts.

Theranostics 2021 21;11(15):7159-7174. Epub 2021 May 21.

Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen.

Glioblastoma (GBM) is a devastating cancer with basically no curative treatment. Even with aggressive treatment, the median survival is disappointing 14 months. Surgery remains the key treatment and the postoperative survival is determined by the extent of resection. Read More

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Discovery of dual targeting PEGylated BG-P-TAT to norepinephrine transporter (NET) and thyrointegrin αvβ3 in the treatment of neuroblastoma.

Bioorg Med Chem 2021 Jun 17;43:116278. Epub 2021 Jun 17.

Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, United States. Electronic address:

Polymer-drug conjugates are growing in interest as novel anticancer agents for targeted cancer therapy. The aim of this study was to synthesize a poly(ethylene glycol) (PEG) conjugated anticancer drug for neuroblastoma, which is the most common extracranial solid tumor of childhood and the deadliest tumor of infancy. In our previous studies, we designed and synthesized a dual targeting agent using benzylguanidine (BG) conjugated with the high affinity thyrointegrin αvβ3 antagonist TriAzole Tetraiodothyroacetic acid (TAT) via non-cleavable bonding to PEG400 to make BG-P-TAT and its derivatives as agents against neuroblastoma. Read More

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Optical control of adenosine A receptor function in psoriasis.

Pharmacol Res 2021 Jun 19:105731. Epub 2021 Jun 19.

Pharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, L'Hospitalet de Llobregat, Spain; Neuropharmacology and Pain Group, Neuroscience Program, Institut d'Investigació Biomèdica de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Spain. Electronic address:

Psoriasis is a chronic and relapsing inflammatory skin disease lacking a cure that affects approximately 2% of the population. Defective keratinocyte proliferation and differentiation, and aberrant immune responses are major factors in its pathogenesis. Available treatments for moderate to severe psoriasis are directed to immune system causing systemic immunosuppression over time, and thus concomitant serious side effects (i. Read More

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Regulation of a pentameric ligand-gated ion channel by a semi-conserved cationic-lipid binding site.

J Biol Chem 2021 Jun 19:100899. Epub 2021 Jun 19.

Laboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium. Electronic address:

Pentameric ligand-gated ion channels (pLGICs) are crucial mediators of electrochemical signal transduction in various organisms from bacteria to humans. Lipids play an important role in regulating pLGIC function, yet the structural bases for specific pLGIC-lipid interactions remain poorly understood. The bacterial channel ELIC recapitulates several properties of eukaryotic pLGICs, including activation by the neurotransmitter GABA, and binding and modulation by lipids, offering a simplified model system for structure-function relationship studies. Read More

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Anchor-Locker Binding Mechanism of the Coronavirus Spike Protein to Human ACE2: Insights from Computational Analysis.

J Chem Inf Model 2021 Jun 22. Epub 2021 Jun 22.

Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

COVID-19 has emerged as the most serious international pandemic in early 2020 and the lack of comprehensive knowledge in the recognition and transmission mechanisms of this virus hinders the development of suitable therapeutic strategies. The specific recognition during the binding of the spike glycoprotein (S protein) of coronavirus to the angiotensin-converting enzyme 2 (ACE2) in the host cell is widely considered the first step of infection. However, detailed insights on the underlying mechanism of dynamic recognition and binding of these two proteins remain unknown. Read More

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Simultaneous enrichment and separation of neutral and sialyl glycopeptides of SARS-CoV-2 spike protein enabled by dual-functionalized Ti-IMAC material.

Anal Bioanal Chem 2021 Jun 21. Epub 2021 Jun 21.

School of Pharmacy, University of Wisconsin-Madison, 5125 Rennebohm Hall, 777 Highland Avenue, Madison, WI, 53705, USA.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a serious threat to human health all over the world. The development of effective vaccines has been focusing on the spike (S) glycoprotein, which mediates viral invasion to human cells through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor. In this work, we perform analytical characterization of N- and O-linked glycosylation of the SARS-CoV-2 S glycoprotein. Read More

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A radioiodinated FR-β-targeted tracer with improved pharmacokinetics through modification with an albumin binder for imaging of macrophages in AS and NAFL.

Eur J Nucl Med Mol Imaging 2021 Jun 21. Epub 2021 Jun 21.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 4221-116 Xiang'An South Rd, Xiamen, 361102, China.

Purpose: The formation of advanced plaques, which is characterized by the uninterrupted aggregation of macrophages with high expression of folate receptor-β (FR-β), is observed in several concomitant metabolic syndromes. The objective of this study was to develop a novel FR-β-targeted single-photon emission computed tomography (SPECT) radiotracer and validate its application to the noninvasive detection of atherosclerosis (AS) plaque and non-alcoholic fatty liver (NAFL).

Methods: Two radioiodinated probes, [I]IPBF and [I]IBF, were developed, and cell uptake studies were used to identify their specific targets for activated macrophages. Read More

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An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency.

Sci Rep 2021 Jun 21;11(1):12987. Epub 2021 Jun 21.

Department of Public Health, Kobe University Graduate School of Health Sciences, Kobe, Japan.

Dengue virus (DENV), from the genus flavivirus of the family flaviviridae, causes serious health problems globally. Human monoclonal antibodies (HuMAb) can be used to elucidate the mechanisms of neutralization and antibody-dependent enhancement (ADE) of DENV infections, leading to the development of a vaccine or therapeutic antibodies. Here, we generated eight HuMAb clones from an Indonesian patient infected with DENV. Read More

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Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2.

Nat Commun 2021 06 21;12(1):3802. Epub 2021 Jun 21.

Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting achieved sub-nanomolar affinity to RBD. Read More

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Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain.

Nat Commun 2021 06 21;12(1):3815. Epub 2021 Jun 21.

Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Since the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short complementarity-determining region (CDR) H3. Germline-encoded sequence motifs in heavy chain CDRs H1 and H2 have a major function, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, is not clear. Read More

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Elucidation of the molecular interactions that enable stable assembly and structural diversity in multicomponent immune receptors.

Proc Natl Acad Sci U S A 2021 Jun;118(26)

Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158

Multicomponent immune receptors are essential complexes in which distinct ligand-recognition and signaling subunits are held together by interactions between acidic and basic residues of their transmembrane helices. A 2:1 acidic-to-basic motif in the transmembrane domains of the subunits is necessary and sufficient to assemble these receptor complexes. Here, we study a prototype for these receptors, a DAP12-NKG2C 2:1 heterotrimeric complex, in which the two DAP12 subunits each contribute a single transmembrane Asp residue, and the NKG2C subunit contributes a Lys to form the complex. Read More

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Molecular and biological characterization of influenza A viruses isolated from human fecal samples.

Infect Genet Evol 2021 Jun 18:104972. Epub 2021 Jun 18.

Biomedical Research Center, Qatar University, Doha 2713, Qatar; Biomedical Sciences, College of Health Sciences-QU Health, Qatar University, Doha 2713, Qatar. Electronic address:

Human influenza viruses are occasionally detected in the stools of influenza patients.

Objectives: Here, we investigated the molecular and biological characteristics of intestinal influenza viruses and their potential role in virus transmission.

Methods: Fecal samples were first screened for the presence of influenza viral RNA using RT-qPCR. Read More

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Intrinsic differences in the mechanisms of Tie2 binding to angiopoietins exploited by directed evolution to create an Ang2-selective ligand-trap.

J Biol Chem 2021 Jun 18:100888. Epub 2021 Jun 18.

Department of Molecular & Cell Biology, and Department of Cardiovascular Sciences, University of Leicester, University Road, Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 7RH UK. Electronic address:

Angiopoietins Ang1 and Ang2 are secreted ligands for the endothelial receptor tyrosine kinase Tie2 essential for vascular development and maintenance. Ang1 acts as an agonist to maintain normal vessel function, whereas Ang2 acts as a Tie2 antagonist. Ang2 is increased in macular edema, sepsis, and other conditions, in which it blocks Ang1-mediated signaling, causing vascular dysfunction and contributing to disease pathology. Read More

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High-affinity P2Y2 and low-affinity P2X7 receptor interaction modulates ATP-mediated calcium signaling in murine osteoblasts.

PLoS Comput Biol 2021 Jun 21;17(6):e1008872. Epub 2021 Jun 21.

Department of Physiology, McGill University, Montreal, Canada.

The P2 purinergic receptor family implicated in many physiological processes, including neurotransmission, mechanical adaptation and inflammation, consists of ATP-gated non-specific cation channels P2XRs and G-protein coupled receptors P2YRs. Different cells, including bone forming osteoblasts, express multiple P2 receptors; however, how P2X and P2Y receptors interact in generating cellular responses to various doses of [ATP] remains poorly understood. Using primary bone marrow and compact bone derived osteoblasts and BMP2-expressing C2C12 osteoblastic cells, we demonstrated conserved features in the P2-mediated Ca2+ responses to ATP, including a transition of Ca2+ response signatures from transient at low [ATP] to oscillatory at moderate [ATP], and back to transient at high [ATP], and a non-monotonic changes in the response magnitudes which exhibited two troughs at 10-4 and 10-2 M [ATP]. Read More

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Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines.

Proteins 2021 Jun 21. Epub 2021 Jun 21.

Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

We have shown that water-soluble variants of the human mu opioid receptor (wsMOR) containing a reduced number of hydrophobic residues at the lipid-facing residues of the transmembrane (TM) helices can be expressed in E. coli. In this study we tested the consequences of increasing the number of mutations on the surface of the transmembrane domain on the receptor's aqueous solubility and ligand binding properties, along with mutation of 11 cysteine residues regardless of their solvent exposure value and location in the protein. Read More

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Pro12Ala polymorphism of peroxisome proliferator activated receptor gamma 2 may be associated with adverse neurodevelopment in European preterm babies.

Brain Behav 2021 Jun 21. Epub 2021 Jun 21.

Department of Perinatal Imaging and Health, Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Introduction: Prematurity is the leading cause of death and disability in children under 5 years of age. Understanding the molecular mechanisms of the biological processes involved in preterm brain injury may help develop novel neuroprotective treatment strategies. A growing body of evidence suggest that peroxisome proliferator-activated receptor gamma (PPARγ) signaling is associated with inhibited brain development in preterm babies. Read More

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Effect of thymoquinone on high fat diet and STZ-induced experimental type 2 diabetes: A mechanistic insight by in vivo and in silico studies.

J Food Biochem 2021 Jun 21:e13807. Epub 2021 Jun 21.

Pharmaceutical Chemistry & Pharmacognosy Department, Unaizah College of Pharmacy, Qassim University, Unaizah, Saudi Arabia.

The aim was to investigate whether thymoquinone (TQ) attenuates hyperglycemia-induced insulin resistance in experimental type 2 diabetes. Type 2 diabetes mellitus (T2DM) was induced by injection of streptozotocin (STZ, 40 mg/kg) in high fat diet (HFD) rats. The levels of glucose, insulin, area under curve (AUC) of glucose, lipid profile parameters, homeostasis model assessment of insulin resistance (HOMA-IR), peroxisome proliferator-activated receptor-γ (PPARγ), and dipeptidyl peptidase peptidase-IV (DPP-IV) were evaluated in HFD + STZ-induced type 2 diabetic rats. Read More

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L a potential source of traditional medicine: chemometric analysis, and study.

J Biomol Struct Dyn 2021 Jun 21:1-17. Epub 2021 Jun 21.

Postgraduate Department of Zoology, Utkal University, Bhubaneswar, India.

'Mayurbhanj is the ethnic dominant tribal population district in Odisha, India. The triabl's of Mayurbhanj depends on traditional medicines since time immemorial for health-related issues. Due to the imperative ethnic claim of traditional healers, the financial stringency of the patient community and the necessity to produce a better therapeutic effect has led to investigate ethno zoological sources and to find out the biochemical moiety responsible for the healing process. Read More

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New insights on the role of vascular endothelial growth factor in biliary pathophysiology.

JHEP Rep 2021 Jun 4;3(3):100251. Epub 2021 Feb 4.

Section of Digestive Diseases, Liver Center, Yale University, New Haven, CT, USA.

The family of vascular endothelial growth factors (VEGFs) includes 5 members (VEGF-A to -D, and placenta growth factor), which regulate several critical biological processes. VEGF-A exerts a variety of biological effects through high-affinity binding to tyrosine kinase receptors (VEGFR-1, -2 and -3), co-receptors and accessory proteins. In addition to its fundamental function in angiogenesis and endothelial cell biology, VEGF/VEGFR signalling also plays a role in other cell types including epithelial cells. Read More

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Production of the Receptor-binding Domain of the Viral Spike Proteins from 2003 and 2019 SARS CoVs and the Four Common Human Coronaviruses for Serologic Assays and Inhibitor Screening.

Bio Protoc 2021 May 20;11(10):e4026. Epub 2021 May 20.

Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, United States.

The recombinant receptor-binding domain (RBD) of the viral spike protein from SARS-CoV-1 and 2 are reliable antigens for detecting viral-specific antibodies in humans. We and others have shown that the levels of RBD-binding antibodies and SARS-CoV-2 neutralizing antibodies in patients are correlated. Here, we report the expression and purification of properly folded RBD proteins from SARS and common-cold HCoVs in mammalian cells. Read More

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