17,939 results match your criteria tam

2D-quantitative structure-activity relationships model using PLS method for anti-malarial activities of anti-haemozoin compounds.

Malar J 2021 Jun 11;20(1):264. Epub 2021 Jun 11.

Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: Emergence of cross-resistance to current anti-malarial drugs has led to an urgent need for identification of potential compounds with novel modes of action and anti-malarial activity against the resistant strains. One of the most promising therapeutic targets of anti-malarial agents related to food vacuole of malaria parasite is haemozoin, a product formed by the parasite through haemoglobin degradation.

Methods: With this in mind, this study developed two-dimensional-quantitative structure-activity relationships (QSAR) models of a series of 21 haemozoin inhibitors to explore the useful physicochemical parameters of the active compounds for estimation of anti-malarial activities. Read More

View Article and Full-Text PDF

The effect of body posture on resting-state functional connectivity.

Brain Connect 2021 Jun 11. Epub 2021 Jun 11.

Stanford University, 6429, Department of Psychiatry & Behavioral Sciences, Stanford, California, United States;

Introduction: An important but under-investigated confound of functional MRI (fMRI) is body posture. Although it is well-established that body position changes cerebral blood flow, the amount of cerebrospinal fluid in the brain, intracranial pressure, and even the firing rate of certain cell types, there is currently no study that directly examines its effect on fMRI measurements. Moreover, fMRI is typically done in a supine position, which often does not correspond to how these processes are performed in everyday settings. Read More

View Article and Full-Text PDF

miR-498 inhibits autophagy and M2-like polarization of tumor-associated macrophages in esophageal cancer via MDM2/ATF3.

Epigenomics 2021 Jun 11. Epub 2021 Jun 11.

Department of Anatomy, School of Basic Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, PR China.

Structured abstract To elucidate the effect of miRNA (miR)-498 on autophagy and M2-like macrophage polarization in esophageal cancer. Autophagy was evaluated in esophageal cancer. Macrophage markers specific for M1- or M2-like phenotype were determined. Read More

View Article and Full-Text PDF

Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy.

Nat Commun 2021 06 10;12(1):3530. Epub 2021 Jun 10.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.

Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observe MAO-A induction in mouse and human TAMs. Read More

View Article and Full-Text PDF

Direct Integration of Strained-Pt Catalysts into Proton-Exchange-Membrane Fuel Cells with Atomic Layer Deposition.

Adv Mater 2021 Jun 10:e2007885. Epub 2021 Jun 10.

Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA.

The design and fabrication of lattice-strained platinum catalysts achieved by removing a soluble core from a platinum shell synthesized via atomic layer deposition, is reported. The remarkable catalytic performance for the oxygen reduction reaction (ORR), measured in both half-cell and full-cell configurations, is attributed to the observed lattice strain. By further optimizing the nanoparticle geometry and ionomer/carbon interactions, mass activity close to 0. Read More

View Article and Full-Text PDF

Programmed Cell Death 10 Mediated CXCL2-CXCR2 Signaling in Regulating Tumor-Associated Microglia/Macrophages Recruitment in Glioblastoma.

Front Immunol 2021 24;12:637053. Epub 2021 May 24.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Programmed cell death 10 (PDCD10) plays a crucial role in regulating tumor phenotyping, especially in glioblastoma (GBM). Glioma-associated microglia/macrophages (GAMs) in tumor pathological microenvironment contribute to GBM progression. We previously found that the infiltration of GAMs was associated with PDCD10 expression in GBM patients. Read More

View Article and Full-Text PDF

Regulation of the one carbon folate cycle as a shared metabolic signature of longevity.

Nat Commun 2021 06 9;12(1):3486. Epub 2021 Jun 9.

Max Planck Institute for Biology of Ageing, Cologne, Germany.

The metabolome represents a complex network of biological events that reflects the physiologic state of the organism in health and disease. Additionally, specific metabolites and metabolic signaling pathways have been shown to modulate animal ageing, but whether there are convergent mechanisms uniting these processes remains elusive. Here, we used high resolution mass spectrometry to obtain the metabolomic profiles of canonical longevity pathways in C. Read More

View Article and Full-Text PDF

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.

Nat Commun 2021 06 9;12(1):3505. Epub 2021 Jun 9.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Read More

View Article and Full-Text PDF

Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors.

Endocrinol Metab (Seoul) 2021 Jun 8. Epub 2021 Jun 8.

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Background: The occurrence of Graves' disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors.

Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Read More

View Article and Full-Text PDF

Mammalian cells use the autophagy process to restrict avian influenza virus replication.

Cell Rep 2021 Jun;35(10):109213

State Key Laboratory for Emerging Infectious Diseases, InnoHK Centre for Virology, Vaccinology, and Therapeutics, and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. Electronic address:

Host adaptive mutations in the influenza A virus (IAV) PB2 protein are critical for human infection, but their molecular action is not well understood. We observe that when IAV containing avian PB2 infects mammalian cells, viral ribonucleoprotein (vRNP) aggregates that localize to the microtubule-organizing center (MTOC) are formed. These vRNP aggregates resemble LC3B-associated autophagosome structures, with aggresome-like properties, in that they cause the re-distribution of vimentin. Read More

View Article and Full-Text PDF

FAM13A as potential therapeutic target in modulating TGF-beta-induced airway tissue remodeling in COPD.

Am J Physiol Lung Cell Mol Physiol 2021 06 9. Epub 2021 Jun 9.

Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.

Genome-wide association studies have shown that a gene variant in the Family with Sequence Similarity 13, Member A (FAM13A) is strongly associated with reduced lung function and the appearance of respiratory symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD). A key player in smoking-induced tissue injury and airway remodeling is the transforming growth factor β1 (TGFβ1). To determine the role of FAM13A in TGFβ1 signaling, FAM13A-/- airway epithelial cells were generated using CRISPR-Cas9, while over-expression of FAM13A was achieved using lipid nanoparticles. Read More

View Article and Full-Text PDF

Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema.

Nat Commun 2021 06 8;12(1):3460. Epub 2021 Jun 8.

Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. Read More

View Article and Full-Text PDF

Iron status of full-term infants in early infancy is not associated with maternal ferritin levels nor infant feeding practice.

Br J Nutr 2021 Jun 9:1-20. Epub 2021 Jun 9.

Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong.

Iron deficiency (ID) in early life is associated with morbidities. Most fetal iron required for infant growth is acquired in the third trimester from maternal iron store. However, how prenatal iron level affects ferritin level in early infancy remains controversial. Read More

View Article and Full-Text PDF

Scalable Production of Lipid Nanoparticles Containing Amphotericin B.

Langmuir 2021 Jun 8. Epub 2021 Jun 8.

Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.

Lipid-based formulations have been developed to improve stability profiles, tolerability, and toxicity profiles of small molecule drugs. However, manufacture of such formulations involving lipophilic compounds can be labor-intensive and difficult to scale because of solubility and solvent compatibility issues. We have developed a rapid and scalable approach using rapid-mixing techniques to generate homogeneous lipid nanoparticle (LNP) formulations of siRNA, triglycerides, and hydrophilic weak-base drugs. Read More

View Article and Full-Text PDF

Contrasting Internet Adoption in Early and Advanced Old Age: Does Internet Self-Efficacy Matter?

J Gerontol B Psychol Sci Soc Sci 2021 Jun 8. Epub 2021 Jun 8.

Department of Psychological Ageing Research, Institute of Psychology, Heidelberg University.

Objectives: Understanding why older adults (including those in very old age) use or do not use the Internet can build on the technology acceptance model (TAM). In this cross-sectional study, we translate the TAM to the Internet and assume that perceived usefulness of the Internet (PUI) and perceived ease of use of the Internet (PEUI) will be revealed as major predictors of behavioural intention to use the Internet (BII). Additionally, we consider the role of Internet self-efficacy (ISE) as another major factor for older adults' Internet use. Read More

View Article and Full-Text PDF

Gold-in-copper at low *CO coverage enables efficient electromethanation of CO.

Nat Commun 2021 Jun 7;12(1):3387. Epub 2021 Jun 7.

Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada.

The renewable-electricity-powered CO electroreduction reaction provides a promising means to store intermittent renewable energy in the form of valuable chemicals and dispatchable fuels. Renewable methane produced using CO electroreduction attracts interest due to the established global distribution network; however, present-day efficiencies and activities remain below those required for practical application. Here we exploit the fact that the suppression of *CO dimerization and hydrogen evolution promotes methane selectivity: we reason that the introduction of Au in Cu favors *CO protonation vs. Read More

View Article and Full-Text PDF

Commentary: A Puzzle With Many "Moving" Parts.

Semin Thorac Cardiovasc Surg 2021 Jun 4. Epub 2021 Jun 4.

Divison of Cardiac Surgery, Department of Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address:

View Article and Full-Text PDF

Mutant IDH1 promotes phagocytic function of microglia/macrophages in gliomas by downregulating ICAM1.

Cancer Lett 2021 Jun 5;517:35-45. Epub 2021 Jun 5.

Hugo W. Moser Research Institute at Kennedy Krieger, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Tumor-associated microglia/macrophages (TAMs) are the main innate immune effector cells in malignant gliomas and have both pro- and anti-tumor functions. The plasticity of TAMs is partially dictated by oncogenic mutations in tumor cells. Heterozygous IDH1 mutation is a cancer driver gene prevalent in grade II/III gliomas, and IDH1 mutant gliomas have relatively favorable clinical outcomes. Read More

View Article and Full-Text PDF

Determinants of Catalan public primary care professionals' intention to use digital clinical consultations (eConsulta) in the post-COVID-19 context: optical illusion or permanent transformation?

J Med Internet Res 2021 May 31. Epub 2021 May 31.

Health Department, eHealth Unit, Barcelona, ES.

Background: During lockdown due to the COVID-19 pandemic, telemedicine has become a necessary component of clinical practice for the purpose of providing safer patient care, and it has been used to support the healthcare needs of COVID-19 patients and routine primary care patients alike. However, this change has not been fully consolidated.

Objective: The objective of this study was to analyse the determinants of healthcare professionals' intention to use the eConsulta digital clinical consultations tool in the post-COVID-19 context. Read More

View Article and Full-Text PDF

A Factorial Approach for Optimizing the Design Parameters of a Tissue Attachment Mechanism for Drug Delivery.

IEEE Trans Biomed Eng 2021 Jun 7;PP. Epub 2021 Jun 7.

Biological macromolecule drugs or biologics are not suited for commonly preferred oral delivery due to their intrinsic instability and physical, chemical, or immunological barriers to the gastrointestinal tract. Ingestible capsule robots (ICR) have become a versatile platform, including use for drug delivery applications for various gastrointestinal pathologies with future potential for systemic drug delivery. In this work, a tissue attachment mechanism (TAM) for a drug delivery ICR is introduced that can facilitate a non-invasive systemic delivery of unaltered biologics via direct injection through the insensate layers of the small intestine. Read More

View Article and Full-Text PDF

A Real-World Examination of Embolic Protection Devices for Transcatheter Aortic Valve Replacement.

Circulation 2021 Jun 7;143(23):2241-2243. Epub 2021 Jun 7.

Division of Cardiology, Schulich Heart Program, Department of Medicine (H.C.W.), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

View Article and Full-Text PDF

UK IBD Twin Registry: Concordance and Environmental Risk Factors of Twins with IBD.

Dig Dis Sci 2021 Jun 7. Epub 2021 Jun 7.

Department of Gastroenterology, Royal London Hospital, Whitechapel Rd, Whitechapel, London, E1 1FR, UK.

Background And Aims: Twin studies have long been used to infer heritability. Within the 'omics era, twin cohorts have even greater research potential. This study describes the formation of the UK IBD Twin Registry and analysis of concordance and environmental factors. Read More

View Article and Full-Text PDF

An Expert Elicitation on the Effects of a Ban on Menthol Cigarettes and Cigars in the United States.

Nicotine Tob Res 2021 Jun 7. Epub 2021 Jun 7.

Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Introduction: The US FDA announced its intention to ban menthol in cigarettes. However, information is needed on how a federal ban would affect population health. We conducted an expert elicitation to gauge the impact of a menthol cigarette and cigar ban in the US. Read More

View Article and Full-Text PDF

Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study.

JAMA Neurol 2021 Jun 7. Epub 2021 Jun 7.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: The neurodevelopmental risks of fetal exposure are uncertain for many antiseizure medications (ASMs).

Objective: To compare children at 2 years of age who were born to women with epilepsy (WWE) vs healthy women and assess the association of maximum ASM exposure in the third trimester and subsequent cognitive abilities among children of WWE.

Design, Setting, And Participants: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter investigation of pregnancy outcomes that enrolled women from December 19, 2012, to January 13, 2016, at 20 US epilepsy centers. Read More

View Article and Full-Text PDF

pH-Controlled Protein Orthogonal Ligation Using Asparaginyl Peptide Ligases.

J Am Chem Soc 2021 Jun 7. Epub 2021 Jun 7.

School of Biological Sciences, Nanyang Technological University, Singapore 637551.

Peptide asparaginyl ligases (PALs) catalyze transpeptidation at the Asn residue of a short Asn-Xaa-Xaa tripeptide motif. Due to their high catalytic activity toward the P1-Asn substrates at around neutral pH, PALs have been used extensively for peptide ligation at asparaginyl junctions. PALs also bind to aspartyl substrates, but only when the COOH of P1-Asp remains in its neutral, protonated form, which usually requires an acidic pH. Read More

View Article and Full-Text PDF

Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy.

Front Oncol 2021 20;11:668731. Epub 2021 May 20.

Center for Surgical Science, Zealand University Hospital, Køge, Denmark.

Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood. Read More

View Article and Full-Text PDF

Solid-phase fluorescent BODIPY-peptide synthesis dipyrrin construction.

Chem Sci 2020 Sep 24;11(41):11266-11273. Epub 2020 Sep 24.

Department of Chemistry, Hong Kong Baptist University Kowloon Hong Kong SAR China

Traditional fluorescent peptide chemical syntheses hinge on the use of limited fluorescent/dye-taggable unnatural amino acids and entail multiple costly purifications. Here we describe a facile and efficient protocol for construction of dipyrrins on the N-terminus with 20 natural and five unnatural amino acids and the lysine's side chain of selected peptides/peptide drugs through Fmoc-based solid-phase peptide synthesis. The new strategy enables the direct formation of boron-dipyrromethene (BODIPY)-peptide conjugates from simple aldehyde and pyrrole derivatives without pre-functionalization, and only requires a single-time chromatographic purification at the final stage. Read More

View Article and Full-Text PDF
September 2020

Sweat the Fall Stuff: Physical Activity Moderates the Association of White Matter Hyperintensities With Falls Risk in Older Adults.

Front Hum Neurosci 2021 21;15:671464. Epub 2021 May 21.

Aging, Mobility, and Cognitive Neuroscience Laboratory, The University of British Columbia, Vancouver, BC, Canada.

Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Read More

View Article and Full-Text PDF

Critical Role of LOX-1-PCSK9 Axis in the Pathogenesis of Atheroma Formation and Its Instability.

Heart Lung Circ 2021 Jun 3. Epub 2021 Jun 3.

Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA. Electronic address:

Cardiovascular disease (CVD) is a major contributor to annual deaths globally. Atherosclerosis is a prominent risk factor for CVD. Although significant developments have been recently made in the prevention and treatment, the molecular pathology of atherosclerosis remains unknown. Read More

View Article and Full-Text PDF

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study.


Colorectal Dis 2020 Dec 18;22(12):2288-2297. Epub 2020 Sep 18.

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Read More

View Article and Full-Text PDF
December 2020