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Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models.

Blood Adv 2021 Dec 6. Epub 2021 Dec 6.

University of California, San Francisco, San Francisco, California, United States.

CD70 is a member of the tumor necrosis factor (TNF) receptor superfamily. Emerging data indicate that CD70 may be a suitable target for various malignancies. We investigated the expression of CD70 in cutaneous and systemic T cell lymphomas; and conducted pre-clinical studies of SGN-CD70A, a CD70-directed antibody-drug conjugate, using patient-derived cutaneous T cell lymphoma (CTCL PDX) models. Read More

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December 2021

Pig farm vaccination against classical swine fever reduces the risk of transmission from wild boar.

Prev Vet Med 2021 Dec 1;198:105554. Epub 2021 Dec 1.

Division of Transboundary Animal Disease Research, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.

In 2018, classical swine fever (CSF) re-emerged in the Gifu Prefecture, central Japan, causing an on-going outbreak among wild boars and domestic pigs in the country. Consequently, oral vaccination for wild boar and compulsory vaccination for pig farms started in 2019. We have previously shown that, before vaccination in the Gifu Prefecture, the presence of CSF-infected wild boar near pig farms increased the risk of CSF transmission. Read More

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December 2021

Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets.

Atherosclerosis 2021 Nov 26;340:12-22. Epub 2021 Nov 26.

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA , 22908, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA. Electronic address:

Background And Aims: The atherosclerotic plaque microenvironment is highly complex, and selective agents that modulate plaque stability are not yet available. We sought to develop a scRNA-seq analysis workflow to investigate this environment and uncover potential therapeutic approaches. We designed a user-friendly, reproducible workflow that will be applicable to other disease-specific scRNA-seq datasets. Read More

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November 2021

UV-guided isolation of enantiomeric polyacetylenes from Bupleurum scorzonerifolium Willd. with inhibitory effects against LPS-induced NO release in BV-2 microglial cells.

Bioorg Chem 2021 Nov 29;119:105521. Epub 2021 Nov 29.

Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang 110142, People's Republic of China. Electronic address:

UV-guided fractionation led to the isolation of thirteen new polyacetylenes (1-13) from the roots of Bupleurum scorzonerifolium Willd. All polyacetylenes were analyzed as racemates since the lack of optical activity and Cotton effects in the ECD spectra. The sequent chiral-phase HPLC resolution successfully gave twelve pairs of enantiomers 1a/1b and 3a/3b-13a/13b. Read More

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November 2021

Vitamin E and preterm infants.

Free Radic Biol Med 2021 Dec 3. Epub 2021 Dec 3.

Division of Neonatology, Department of Pediatrics, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan.

In evaluating vitamin E (VE) nutritional status of preterm infants, it is essential that any data should be compared with those of healthy term infants, and never with those of adults. Moreover, it should be evaluated in terms of gestational age (GA), not birth weight (BW), because placental transfer of most nutrients from mother to fetus is dependent on GA, not BW. Judging from the limited data during the last 75 years, there was no significant correlation between GA and VE concentrations in circulation or in the red blood cells (RBCs), leukocytes, and buccal mucosal cells. Read More

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December 2021

Hormesis and neural stem cells.

Free Radic Biol Med 2021 Dec 3. Epub 2021 Dec 3.

Neurology and Biochemistry, Georgetown University Medical Center; Washington, DC, 20057, USA. Electronic address:

This paper provides a detailed identification and assessment of hormetic dose responses in neural stem cells (NSCs) as identified in a number of animal models and human tissues, with particular emphasis on cell proliferation and differentiation. Hormetic dose responses were commonly observed following administration of a number of agents, including dietary supplements [e.g. Read More

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December 2021

Design and Synthesis of a Star-Like Polymeric Micelle Modified with AS1411 Aptamer for Targeted Delivery of Camptothecin for Cancer Therapy.

Int J Pharm 2021 Dec 3:121346. Epub 2021 Dec 3.

Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Improving of tumor targeting and decreasing side effects at normal cells of antitumor drugs are necessary to promote the cancer chemotherapy efficacy. Herein, we have synthesized a novel 21-arm star like diblock polymer of β-cyclodextrin-{poly(ε-caprolactone)-poly(2-aminoethylmethacrylate)} which decorated with nucleolin aptamer (AS1411). The diblock polymer was prepared by combined ROP with electron transfer atom transfer radical polymerization (ARGET ATRP) methods followed camptothecin (CPT) encapsulation with high entrapment efficiency (65%). Read More

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December 2021

All layers matter: Innovative three-dimensional epithelium-stroma-endothelium intestinal model for reliable permeability outcomes.

J Control Release 2021 Dec 3. Epub 2021 Dec 3.

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal. Electronic address:

Drug development is an ever-growing field, increasingly requesting reliable in vitro tools to speed up early screening phases, reducing the need for animal experiments. In oral delivery, understanding the absorption pattern of a new drug in the small intestine is paramount. Classical two-dimensional (2D) in vitro models are generally too simplistic and do not accurately represent native tissues. Read More

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December 2021

Identification of novel combined biomarkers in the diagnosis of multiple myeloma.

Hematology 2021 Dec;26(1):964-969

Department of Haematology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.

Purpose: Multiple myeloma (MM) is a haematological malignant disease with a clonal proliferation of plasma cells, and timely surveillance is helpful to improve the survival rate of patients with MM. However, there is a lack of simple and effective biomarkers for the diagnosis, prognosis, and residual disease evaluation of MM.

Material & Methods: In the detection cohort, we used the samples from six newly diagnosed MM patients and six control subjects. Read More

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December 2021

Artemether and aspterric acid induce pancreatic α cells to transdifferentiate into β cells in zebrafish.

Br J Pharmacol 2021 Dec 6. Epub 2021 Dec 6.

Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.

Background And Purpose: Recently, the anti-malarial drug, artemether, and the neurotransmitter γ-aminobutyric acid (GABA) were identified to convert α cells into β-like cells in vivo. However, some of these observations were challenged by other studies. To help address the controversy, we took advantage of zebrafish as a model to perform this study. Read More

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December 2021

Effective and scalable single-cell data alignment with non-linear canonical correlation analysis.

Nucleic Acids Res 2021 Dec 6. Epub 2021 Dec 6.

Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.

Data alignment is one of the first key steps in single cell analysis for integrating multiple datasets and performing joint analysis across studies. Data alignment is challenging in extremely large datasets, however, as the major of the current single cell data alignment methods are not computationally efficient. Here, we present VIPCCA, a computational framework based on non-linear canonical correlation analysis for effective and scalable single cell data alignment. Read More

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December 2021

Hubness reduction improves clustering and trajectory inference in single-cell transcriptomic data.

Bioinformatics 2021 Nov 23. Epub 2021 Nov 23.

Institut Curie, PSL Research University, F-75005 Paris, France.

Motivation: Single-cell RNA-seq (scRNAseq) datasets are characterized by large ambient dimensionality, and their analyses can be affected by various manifestations of the dimensionality curse. One of these manifestations is the hubness phenomenon, i.e. Read More

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November 2021

In Vivo Metabolic Roles of G Proteins of the Gi Family Studied with Novel Mouse Models.

Authors:
Jürgen Wess

Endocrinology 2021 Dec 5. Epub 2021 Dec 5.

Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.

G protein-coupled receptors (GPCRs) are the target of ~30-35% of all FDA-approved drugs. The individual members of the GPCR superfamily couple to one or more functional classes of heterotrimeric G proteins. The physiological outcome of activating a particular GPCR in vivo depends on the pattern of receptor distribution and the type of G proteins activated by the receptor. Read More

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December 2021

Severe asthma: One disease and multiple definitions.

World Allergy Organ J 2021 Nov 19;14(11):100606. Epub 2021 Nov 19.

Allergy and Respiratory Diseases, Department of Internal Medicine (DIMI), IRCCS Policlinico San Martino, University of Genoa, Italy.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Read More

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November 2021

Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication.

PLoS Pathog 2021 Dec 6;17(12):e1010113. Epub 2021 Dec 6.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, P. R. China.

Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. Read More

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December 2021

Budesonide promotes airway epithelial barrier integrity following double-stranded RNA challenge.

PLoS One 2021 6;16(12):e0260706. Epub 2021 Dec 6.

Department of Microbiology and Immunology, University of Rochester, Rochester, New York, United States of America.

Airway epithelial barrier dysfunction is increasingly recognized as a key feature of asthma and other lung diseases. Respiratory viruses are responsible for a large fraction of asthma exacerbations, and are particularly potent at disrupting epithelial barrier function through pattern recognition receptor engagement leading to tight junction dysfunction. Although different mechanisms of barrier dysfunction have been described, relatively little is known about whether barrier integrity can be promoted to limit disease. Read More

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December 2021

Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study.

PLoS Med 2021 Dec 6;18(12):e1003868. Epub 2021 Dec 6.

Department of Surgery and Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.

Background: People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. Read More

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December 2021

Cell competition is driven by Xrp1-mediated phosphorylation of eukaryotic initiation factor 2α.

PLoS Genet 2021 Dec 6;17(12):e1009958. Epub 2021 Dec 6.

Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto, Japan.

Cell competition is a context-dependent cell elimination via cell-cell interaction whereby unfit cells ('losers') are eliminated from the tissue when confronted with fitter cells ('winners'). Despite extensive studies, the mechanism that drives loser's death and its physiological triggers remained elusive. Here, through a genetic screen in Drosophila, we find that endoplasmic reticulum (ER) stress causes cell competition. Read More

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December 2021

Loss of an Intimin-Like Protein Encoded on a Uropathogenic Pathogenicity Island Reduces Inflammation and Affects Interactions with the Urothelium.

Infect Immun 2021 Dec 6:IAI0027521. Epub 2021 Dec 6.

Department of Microbiology and Immunology, University of Michigan Medical School, 5641 West Medical Center Drive, Ann Arbor, Michigan 48109.

Uropathogenic (UPEC) causes the majority of uncomplicated urinary tract infections (UTI), which affect nearly half of women worldwide. Many UPEC strains encode an annotated intimin-like adhesin () locus in their genome related to a well-characterized virulence factor in diarrheagenic pathotypes. Its role in UPEC uropathogenesis, however, remains unknown. Read More

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December 2021

Acquired clinical immunity to malaria in non-human primates co-infected with and parasites.

Infect Immun 2021 Dec 6:IAI0046421. Epub 2021 Dec 6.

Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya.

Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons (n=8 each), were infected with cercariae to establish chronic infections. Read More

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December 2021

Transcriptomic Analysis of Human Naïve and Primed Pluripotent Stem Cells.

Methods Mol Biol 2022 ;2416:213-237

Centre of Bioinformatics, Institute of Interdisciplinary Studies, University of Allahabad, Prayagraj, India.

Over the last decade, RNA-Sequencing (RNA-Seq) has revolutionized the field of transcriptomics due to its sheer advantage over previous technologies for studying gene expression. Even the domain of stem cell bioinformatics has benefited from these advancements. It has helped look deeper into how the process of pluripotency is maintained by stem cells and how it may be exploited for application in regenerative medicine. Read More

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January 2022

Mapping Chromatin Accessibility in Human Naïve Pluripotent Stem Cells Using ATAC-Seq.

Methods Mol Biol 2022 ;2416:201-211

Department of Biochemistry, McGill University, Montreal, QC, Canada.

Regulatory elements, such as promoters and enhancers, typically show reduced nucleosome occupancy, which is a feature that is commonly referred to as "open chromatin". The distribution of open chromatin sites can provide important clues about the transcription factors and regulatory networks that drive gene expression in a given cell. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a rapid and robust method for mapping open chromatin sites. Read More

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January 2022

Chromatin Profiling of Human Naïve Pluripotent Stem Cells.

Methods Mol Biol 2022 ;2416:181-200

Epigenetics Programme, The Babraham Institute, Cambridge, UK.

Chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-sequencing) facilitates the genome-wide mapping of DNA sequences that are enriched for specific chromatin-binding proteins or histone post-translational modifications. More recently developed chromatin profiling methods called Cleavage Under Targets and Release Using Nuclease (CUT&RUN) and Cleavage Under Targets and Tagmentation (CUT&Tag) have adapted the ChIP-sequencing approach to produce similar data from a smaller amount of starting material, and while overcoming many of the conventional drawbacks of ChIP-sequencing. Here, we present detailed protocols for ChIP-seq, CUT&RUN, and CUT&Tag to profile genome-wide protein-DNA interactions in naïve human pluripotent stem cells. Read More

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January 2022

Profiling DNA Methylation in Human Naïve Pluripotent Stem Cells.

Methods Mol Biol 2022 ;2416:157-180

Laboratory of Nutrition and Metabolic Epigenetics, Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.

DNA methylation represents one of the best characterized epigenetic modifications. In particular, global demethylation is a common feature of epigenetic reprogramming to naïve pluripotency in human and mouse pluripotent stem cells. In parallel to the global changes, several locus-specific changes to the DNA methylation landscape occur and also loss of imprinting has been observed in naïve human pluripotent stem cells. Read More

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January 2022

An Imaging Flow Cytometry Protocol for Studying Immunoregulatory Receptor-Mediated Regulation of Phagocytosis.

Methods Mol Biol 2022 ;2421:201-216

Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.

Advances in flow cytometry have allowed for innovative functional investigations of innate immune cell responses. Imaging flow cytometers combine the imaging capabilities of microscopy with rapid, high-throughput data acquisition attributes of standard flow cytometers. Here, we describe a detailed method for co-expressing stimulatory and inhibitory immunoregulatory receptor-types in AD293 cells and then measuring receptor cross-talk during the regulation of the phagocytic response. Read More

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January 2022

Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation.

Basic Res Cardiol 2021 Dec 6;116(1):64. Epub 2021 Dec 6.

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.

Acute rejection (AR) is an important contributor to graft failure, which remains a leading cause of death after heart transplantation (HTX). The regulation of immune metabolism has become a new hotspot in the development of immunosuppressive drugs. In this study, Increased glucose metabolism of cardiac macrophages was found in patients with AR. Read More

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December 2021

sp. nov., an equol non-producing bacterium isolated from human faeces.

Int J Syst Evol Microbiol 2021 Dec;71(12)

Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Research Center, Tsukuba, Ibaraki 305-0074, Japan.

Two obligately anaerobic, Gram-stain-positive, rod-shaped bacteria were isolated from faecal samples of healthy humans in Japan. 16S rRNA gene sequence analysis indicated that these two strains (8CFCBH1 and 9CBH6) belonged to the genus , which is known as an equol-producing bacterium. The closest neighbours of strain 8CFCBH1 were subsp. Read More

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December 2021

A novel polymerase β inhibitor from phage displayed peptide library augments the anti-tumour effects of temozolomide on colorectal cancer.

J Chemother 2021 Dec 6:1-10. Epub 2021 Dec 6.

Qinhuai Medical District, Jinlin Hospital of Nanjing University, Nanjing, China.

The therapeutic efficacy of TMZ, a common used drug for chemotherapy, is limited by the resistance from colorectal cancer cells. Base excision repair (BER) pathway has been identified as one of the reasons for drug resistance. By blocking Polβ-dependent BER (Base Excision Repair) pathway, the efficacy of TMZ treatment can be improved greatly. Read More

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December 2021

Adaptor SH3BGRL drives autophagy-mediated chemoresistance through promoting PIK3C3 translation and ATG12 stability in breast cancers.

Autophagy 2021 Dec 6:1-19. Epub 2021 Dec 6.

Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Acquired chemotherapy resistance is one of the main culprits in the relapse of breast cancer. But the underlying mechanism of chemotherapy resistance remains elusive. Here, we demonstrate that a small adaptor protein, SH3BGRL, is not only elevated in the majority of breast cancer patients but also has relevance with the relapse and poor prognosis of breast cancer patients. Read More

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December 2021

Metabolic reprograming shapes neutrophil functions in severe COVID-19.

Eur J Immunol 2021 Dec 6. Epub 2021 Dec 6.

Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

To better understand the mechanisms at the basis of neutrophil functions during SARS-CoV-2 we studied patients with severe COVID-19 pneumonia. They had high blood proportion of degranulated neutrophils and elevated plasma levels of myeloperoxidase (MPO), elastase and MPO-DNA complexes, which are typical markers of neutrophil extracellular traps (NET). Their neutrophils display dysfunctional mitochondria, defective oxidative burst, increased glycolysis, glycogen accumulation in the cytoplasm, and increase glycogenolysis. Read More

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December 2021