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Quercetin inhibiting the PD-1/PD-L1 interaction for immune-enhancing cancer chemopreventive agent.

Phytother Res 2021 Sep 24. Epub 2021 Sep 24.

Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, School of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.

Targeting the PD-1/PD-L1 immune checkpoints has achieved significant positive results in the treatment of multiple cancers. Quercetin is one of the most abundant dietary flavonoids found in various vegetables and fruits, and has a wide range of biological activities including immunomodulation. Here we report that quercetin dihydrate was screened and shown to inhibit the PD-1/PD-L1 interaction. Read More

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September 2021

Lrp1 is a host entry factor for Rift Valley fever virus.

Cell 2021 Sep 22. Epub 2021 Sep 22.

Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Current address: Vir Biotechnology, San Francisco, CA, USA.

Rift Valley fever virus (RVFV) is a zoonotic pathogen with pandemic potential. RVFV entry is mediated by the viral glycoprotein (Gn), but host entry factors remain poorly defined. Our genome-wide CRISPR screen identified low-density lipoprotein receptor-related protein 1 (mouse Lrp1/human LRP1), heat shock protein (Grp94), and receptor-associated protein (RAP) as critical host factors for RVFV infection. Read More

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September 2021

Interplay of Trypanosome Lytic Factor and innate immune cells in the resolution of cutaneous Leishmania infection.

PLoS Pathog 2021 Sep 24;17(9):e1008768. Epub 2021 Sep 24.

Department of Biology, Hunter College, City University of New York, New York, New York, United States of America.

Trypanosome Lytic Factor (TLF) is a primate-specific high-density lipoprotein (HDL) complex that, through the cation channel-forming protein apolipoprotein L-1 (APOL1), provides innate immunity to a select kinetoplastid parasites. The immunoprotective effects of TLF have been extensively investigated in the context of its interaction with the extracellular protozoan Trypanosoma brucei brucei, to which it confers sterile immunity. We previously showed that TLF could act against intracellular pathogen Leishmania, and here we dissected the role of TLF and its synergy with host-immune cells. Read More

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September 2021

PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta.

Development 2021 Oct 24;148(19). Epub 2021 Sep 24.

Department of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.

The therian-specific gene paternally expressed 10 (Peg10) plays an essential role in placenta formation: Peg10 knockout mice exhibit early embryonic lethality as a result of severe placental defects. The PEG10 protein exhibits homology with long terminal repeat (LTR) retrotransposon GAG and POL proteins; therefore, we generated mice harboring a mutation in the highly conserved viral aspartic protease motif in the POL-like region of PEG10 because this motif is essential for the life cycle of LTR retrotransposons/retroviruses. Intriguingly, frequent perinatal lethality, not early embryonic lethality, was observed with fetal and placental growth retardation starting mid-gestation. Read More

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October 2021

Faecalibacterium Prausnitzii Attenuates DSS-Induced Colitis by Inhibiting the Colonization and Pathogenicity of Candida Albicans.

Mol Nutr Food Res 2021 Sep 24:e2100433. Epub 2021 Sep 24.

Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Scope: Intestinal commensal microbiota interactions play critical roles in the inflammatory bowel disease(IBD) development. Candida albicans(CA) can aggravate intestinal inflammation; however, whether Faecalibacterium prausnitzii(FP) can antagonize CA is unknown.

Methods And Results: CA were cocultured with bacteria (FP and E. Read More

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September 2021

ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling.

J Cell Sci 2021 Sep 24. Epub 2021 Sep 24.

Max-Delbrueck-Center for Molecular Medicine, 13125 Berlin, Germany.

Sortilin is a neuronal receptor for apolipoprotein E. Sortilin-dependent uptake of lipidated apoE promotes conversion of polyunsaturated fatty acids (PUFA) into neuromodulators that induce anti-inflammatory gene expression in the brain. This neuroprotective pathway works with apoE3 but is lost with apoE4, the main risk factor for Alzheimer's disease (AD). Read More

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September 2021

Reduction of cortical parvalbumin expressing GABAergic interneurons in a rodent hyperoxia model of preterm birth brain injury with deficits in social behavior and cognition.

Development 2021 Sep 24. Epub 2021 Sep 24.

Department of Neonatology, Charité - Universitätsmedizin Berlin, Germany.

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the mechanisms underlying are not known. In a translational hyperoxia model, exposing mice pups at age P5 to 80% oxygen for 48 hours to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin expressing interneurons until adulthood. Read More

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September 2021

Interaction between Chitosan and Chloroquine against and Using In-Vivo and In-Vitro Tests.

Iran J Parasitol 2021 Apr-Jun;16(2):261-269

Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: The use of antimalarial drugs with number of compounds in combination form may potentiate each other's activity.

Methods: This study was conducted in the School of Public Health, Tehran University of Medical Sciences, Tehran, Iran in 2018. It was based on two methods including in vivo and in vitro tests with aim of considering interaction between chitosan and chloroquine against and parasites using different ratios of the agents with ED50 and IC50 baselines. Read More

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The Paradox of a Phagosomal Lifestyle: How Innate Host Cell- Interactions Lead to a Progressive Chronic Disease.

Front Immunol 2021 7;12:728848. Epub 2021 Sep 7.

Snyder Institute for Chronic Diseases, Departments of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine and Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.

Intracellular phagosomal pathogens represent a formidable challenge for innate immune cells, as, paradoxically, these phagocytic cells can act as both host cells that support pathogen replication and, when properly activated, are the critical cells that mediate pathogen elimination. Infection by parasites of the genus provides an excellent model organism to investigate this complex host-pathogen interaction. In this review we focus on the dynamics of infection and the host innate immune response, including the impact of the adaptive immune response on phagocytic host cell recruitment and activation. Read More

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September 2021

The conserved fertility factor SPACA4/Bouncer has divergent modes of action in vertebrate fertilization.

Proc Natl Acad Sci U S A 2021 09;118(39)

Research Institute of Molecular Pathology, Vienna BioCenter, Campus-Vienna-Biocenter 1, 1030 Vienna, Austria;

Fertilization is the fundamental process that initiates the development of a new individual in all sexually reproducing species. Despite its importance, our understanding of the molecular players that govern mammalian sperm-egg interaction is incomplete, partly because many of the essential factors found in nonmammalian species do not have obvious mammalian homologs. We have recently identified the lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) protein Bouncer as an essential fertilization factor in zebrafish [S. Read More

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September 2021

Comparative gene expression analysis for pre-osteoblast MC3T3-E1 cells under non-adhesive culture toward osteocyte differentiation.

J Biosci Bioeng 2021 Sep 21. Epub 2021 Sep 21.

Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8507, Japan; Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Osteocytes play an important role to modulate the bone remodeling and are also known as terminally differentiated cells originated from the osteoblast precursor cells, but its differentiation mechanism remains unclear. Since an efficient in vitro method to evoke the osteocyte differentiation from the osteoblast precursor cells has not been established, we conducted the comparative gene expression analysis for mouse pre-osteoblast MC3T3-E1 cells in order to elucidate the key factors to induce the osteocyte differentiation from the pre-osteoblast cells. In this study, we prepared four different culture environments by modulating their cell-substrate interaction and cell-cell interaction; (i) low and (ii) high cell density on the adhesive culture models, and (iii) low and (iv) high cell density on the non-adhesive floating culture models. Read More

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September 2021

Early and Late Corrections in Mouse Models of Autism Spectrum Disorder.

Biol Psychiatry 2021 Jul 29. Epub 2021 Jul 29.

Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon, South Korea; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea. Electronic address:

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and repetitive symptoms. A key feature of ASD is early-life manifestations of symptoms, indicative of early pathophysiological mechanisms. In mouse models of ASD, increasing evidence indicates that there are early pathophysiological mechanisms that can be corrected early to prevent phenotypic defects in adults, overcoming the disadvantage of the short-lasting effects that characterize adult-initiated treatments. Read More

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CONSEQUENCES OF mTOR INHIBITION ON AAV HEPATIC TRANSDUCTION EFFICACY.

Hum Gene Ther 2021 Sep 24. Epub 2021 Sep 24.

Foundation for Applied Medical Research, Av Pio XII 55, Pamplona, Spain, 31008;

The efficiency of recombinant Adeno-associated virus vectors (AAV) transducing host cells is very low, limiting their therapeutic potential in patients. There are several cellular pathways interacting and interfering with the journey of the AAV from the cell surface to the nucleus, opening the possibility to enhance AAV transduction by modifying these interactions. In this study, we explored the results of AAV hepatic transduction when different mTOR inhibitors. Read More

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September 2021

Co-assembled Nanocomplexes of Peptide Neoantigen Adpgk and Toll-like Receptor 9 Agonist CpG ODN for Efficient Colorectal Cancer Immunotherapy.

Int J Pharm 2021 Sep 20:121091. Epub 2021 Sep 20.

The Faculty of Environment and Life, Beijing University of Technology, NO. 100, Pingleyuan, Chaoyang District, Beijing, 100124, People's Republic of China. Electronic address:

Cancer vaccines targeting tumor specific neoantigens derived from nonsynonymous mutations of tumor cells have emerged as an effective approach to induce antitumor T cells responses for personalized cancer immunotherapy. Despite the enormous potential of synthetic peptides as a common modality for neoantigen vaccines, their practical efficacy was limited due to their relatively low immunogenicity. Herein, we modify neoantigen peptide (Adpgk) derived from MC-38 colon carcinoma by supplementing ten consecutive positively-charged lysine (10K-Adpgk) to obtain cationic polypeptide. Read More

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September 2021

Oxidized LDL but not angiotensin II induces cardiomyocyte hypertrophic responses through the interaction between LOX-1 and AT receptors.

J Mol Cell Cardiol 2021 Sep 20. Epub 2021 Sep 20.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biological Science, Fudan University, Shanghai 200032, China. Electronic address:

It is well known that lectin-like oxidized low-density lipoprotein (ox-LDL) and its receptor LOX-1, angiotensin II (AngII) and its type 1 receptor (AT-R) play an important role in the development of cardiac hypertrophy. However, the molecular mechanism is not clear. In this study, we found that ox-LDL-induced cardiac hypertrophy was suppressed by inhibition of LOX-1 or AT1-R but not by AngII inhibition. Read More

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September 2021

Scientific memory from the early nineties; a common project with professors late János Gergely and Anna Erdei.

Biol Futur 2021 Mar 10;72(1):3-5. Epub 2021 Jan 10.

Department of Immunology, MTA-ELTE Immunology Research Group, Eötvös University, Budapest, Hungary.

Based on the findings of common project 29 years ago, the Scandinavian J. of Immunology accepted and published our paper entitled by "FcγR-Dependent Regulation of the Biosynthesis of Complement C3 by Murine Macrophages: the Modulatory Effect of IL-6" (Bajtay et al. in SJI 35:195-201, 1992). Read More

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RNA editing of 5-HT R impairs insulin secretion of pancreatic beta cells via altered store-operated calcium entry.

FASEB J 2021 Oct;35(10):e21929

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Recent studies emphasize the importance of 5-HT2C receptor (5-HT R) signaling in the regulation of energy homeostasis. The 5-HT R is the only G-protein-coupled receptor known to undergo post-transcriptional adenosine to inosine (A-to-I) editing by adenosine deaminase acting on RNA (ADAR). 5-HT R has emerged as an important role in the modulation of pancreatic β cell functions. Read More

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October 2021

Enriched Environment Cues Suggest a New Strategy to Counteract Glioma: Engineered rAAV2-IL-15 Microglia Modulate the Tumor Microenvironment.

Front Immunol 2021 6;12:730128. Epub 2021 Sep 6.

Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.

Several types of cancer grow differently depending on the environmental stimuli they receive. In glioma, exposure to an enriched environment (EE) increases the overall survival rate of tumor-bearing mice, acting on the cells that participate to define the tumor microenvironment. In particular, environmental cues increase the microglial production of interleukin (IL)-15 which promotes a pro-inflammatory (antitumor) phenotype of microglia and the cytotoxic activity of natural killer (NK) cells, counteracting glioma growth, thus representing a virtuous mechanism of interaction between NK cells and microglia. Read More

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September 2021

Transcriptome Analysis of Immune Receptor Activation and Energy Metabolism Reduction as the Underlying Mechanisms in Interleukin-6-Induced Skeletal Muscle Atrophy.

Front Immunol 2021 6;12:730070. Epub 2021 Sep 6.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, National Medical Products Administration Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong, China.

Background: Inflammation may trigger skeletal muscle atrophy induced by cancer cachexia. As a pro-inflammatory factor, interleukin-6 may cause skeletal muscle atrophy, but the underlying molecular mechanisms have not been explored.

Methods: In this experimental study, we used adult male ICR mice, weighing 25 ± 2 g, and the continuous infusion of interleukin-6 into the tibialis anterior muscle to construct a skeletal muscle atrophy model (experimental group). Read More

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September 2021

Microbial Composition and Co-occurrence Patterns in the Gut Microbial Community of Normal and Obese Mice in Response to Astaxanthin.

Front Microbiol 2021 6;12:671271. Epub 2021 Sep 6.

Laboratory of Food Science and Human Health, College of Food Science and Engineering, Ocean University of China, Qingdao, China.

The changes and interaction of gut microbiota, which respond to dietary supplements, play critical roles on improving human health. The modulating effect of astaxanthin on gut microbiota has been reported. However, little is known about the co-occurrence patterns among microbial taxa in response to astaxanthin. Read More

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September 2021

Pharmacological inhibition of MyD88 suppresses inflammation in tubular epithelial cells and prevents diabetic nephropathy in experimental mice.

Acta Pharmacol Sin 2021 Sep 22. Epub 2021 Sep 22.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.

Emerging evidence shows that chronic inflammation mediated by toll-like receptors (TLRs) contributes to diabetic nephropathy. Myeloid differentiation primary-response protein-88 (MyD88) is an essential adapter protein of all TLRs except TLR3 in innate immunity. It is unclear whether MyD88 could be a therapeutic target for diabetic nephropathy. Read More

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September 2021

Autophagic secretion of HMGB1 from cancer-associated fibroblasts promotes metastatic potential of non-small cell lung cancer cells via NFκB signaling.

Cell Death Dis 2021 Sep 22;12(10):858. Epub 2021 Sep 22.

Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Tumor progression requires the communication between tumor cells and tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are major components of stromal cells. CAFs contribute to metastasis process through direct or indirect interaction with tumor cells; however, the underlying mechanism is largely unknown. Read More

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September 2021

Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.

J Immunol 2021 Sep 22. Epub 2021 Sep 22.

Baylor Scott & White Immunology Research, Dallas, TX;

CD40 is a potent activating receptor within the TNFR family expressed on APCs of the immune system, and it regulates many aspects of B and T cell immunity via interaction with CD40 ligand (CD40L; CD154) expressed on the surface of activated T cells. Soluble CD40L and agonistic mAbs directed to CD40 are being explored as adjuvants in therapeutic or vaccination settings. Some anti-CD40 Abs can synergize with soluble monomeric CD40L. Read More

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September 2021

Nuclear speckle specific hnRNP D-like prevents age- and AD-related cognitive decline by modulating RNA splicing.

Mol Neurodegener 2021 Sep 22;16(1):66. Epub 2021 Sep 22.

Institute on Aging and Brain Disorders, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.

Background: Aberrant alternative splicing plays critical role in aging and age-related diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) reportedly regulate RNA splicing process. Whether and how hnRNPs contribute to age-related neurodegenerative diseases, especially Alzheimer's disease (AD), remain elusive. Read More

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September 2021

Receptor and Molecular Mechanism of AGGF1 Signaling in Endothelial Cell Functions and Angiogenesis.

Arterioscler Thromb Vasc Biol 2021 Sep 23:ATVBAHA121316867. Epub 2021 Sep 23.

Departments of Molecular Cardiology and Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, OH (A.A.T., V.P., S.-A.Y., C.F., Q.C., Q.W.).

Objective: Angiogenic factor AGGF1 (angiogenic factor and G-patch and FHA [Forkhead-associated] domain 1) promotes angiogenesis as potently as VEGFA (vascular endothelial growth factor A) and regulates endothelial cell (EC) proliferation, migration, specification of multipotent hemangioblasts and venous ECs, hematopoiesis, and vascular development and causes vascular disease Klippel-Trenaunay syndrome when mutated. However, the receptor for AGGF1 and the underlying molecular mechanisms remain to be defined. Approach and Results: Using functional blocking studies with neutralizing antibodies, we identified α5β1 as the receptor for AGGF1 on ECs. Read More

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September 2021

Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection.

Cell Rep 2021 Sep;36(12):109750

Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China. Electronic address:

The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. Read More

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September 2021

Kainate receptors regulate the functional properties of young adult-born dentate granule cells.

Cell Rep 2021 Sep;36(12):109751

Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurobiology, Northwestern University, Chicago, IL 60611, USA. Electronic address:

Both inhibitory and excitatory neurotransmitter receptors can influence maturation and survival of adult-born neurons in the dentate gyrus; nevertheless, how these two neurotransmitter systems affect integration of new neurons into the existing circuitry is still not fully characterized. Here, we demonstrate that glutamate receptors of the kainate receptor (KAR) subfamily are expressed in adult-born dentate granule cells (abDGCs) and that, through their interaction with GABAergic signaling mechanisms, they alter the functional properties of adult-born cells during a critical period of their development. Both the intrinsic properties and synaptic connectivity of young abDGCs were affected. Read More

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September 2021

Atypical TNF-TNFR superfamily binding interface in the GITR-GITRL complex for T cell activation.

Cell Rep 2021 Sep;36(12):109734

Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a critical regulatory molecule in modulation of T cell immune responses. Here we report the mouse GITR (mGITR) and mGITR ligand (mGITRL) complex structure and find that the binding interface of mGITR and mGITRL is distinct from the typical tumor necrosis factor superfamily (TNFSF)/TNF receptor superfamily (TNFRSF) members. mGITR binds to its ligand with a single domain, whereas the binding interface on mGITRL is located on the side, which is distal from conserved binding sites of TNFSF molecules. Read More

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September 2021

Semi-continuous propagation of influenza A virus and its defective interfering particles: analyzing the dynamic competition to select candidates for antiviral therapy.

J Virol 2021 Sep 22:JVI0117421. Epub 2021 Sep 22.

Max Planck Institute for Dynamics of Complex Technical Systems, Bioprocess Engineering, Magdeburg, Germany.

Defective interfering particles (DIPs) of influenza A virus (IAV) are naturally occurring mutants that comprise an internal deletion in one of their eight viral RNA (vRNA) segments, rendering them propagation-incompetent. Upon co-infection with infectious standard virus (STV), DIPs interfere with STV replication through competitive inhibition. Thus, DIPs are proposed as potent antivirals for treatment of the influenza disease. Read More

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September 2021

Accelerated Discovery of Potent Bioactive anti-TNFα Aptamers by Microbead-Assisted Capillary Electrophoresis (MACE)-SELEX.

Chembiochem 2021 Sep 22. Epub 2021 Sep 22.

The University of Tokyo: Tokyo Daigaku, Department of Life Sciences, Graduate School of Arts and Sciences, 3-8-1, Komaba, Meguro-ku, 153-8902, Tokyo, JAPAN.

Dysregulation of tumor necrosis factor-α (TNFα), a pro-inflammatory cytokine, causes several diseases, making it an important therapeutic target. Here, we identified a novel DNA aptamer against human TNFα using in vitro selection, which included a high exclusion pressure process against non-binding and weak binders through microbead-assisted capillary electrophoresis (MACE) in only 3 rounds. Among the 15 most enriched aptamers, Apt14 exhibited the highest inhibitory activity for the interaction between TNFα and its cognate receptor in mouse L929 cells. Read More

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September 2021