Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium.
View Article and Find Full Text PDFWe identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone , a compound in clinical trials for anti-fibrotic and anti-inflammatory applications , as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry . We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection.
View Article and Find Full Text PDFApplying environmental education in primate range countries is an important long-term activity to stimulate pro-conservation behavior. Within captive settings, mega-charismatic species, such as great apes are often used to increase knowledge and positively influence attitudes of visitors. Here, we evaluate the effectiveness of a short-term video and theater program developed for a Western audience and adapted to rural people living in two villages around Nouabalé-Ndoki National Park, Republic of Congo.
View Article and Find Full Text PDFOcaliva, a synthetic bile acid analog with high affinity for the nuclear bile acid receptor FXR, is effective in treating primary biliary cholangitis, an autoimmune liver disease. It works in patients who fail to respond to or cannot tolerate conventional treatment with the natural bile acid ursodeoxycholic acid (UDCA).
View Article and Find Full Text PDFCommunication between cells in a multicellular organism occurs by the production of ligands (proteins, peptides, fatty acids, steroids, gases, and other low-molecular-weight compounds) that are either secreted by cells or presented on their surface, and act on receptors on, or in, other target cells. Such signals control cell growth, migration, survival, and differentiation. Signaling receptors can be single-span plasma membrane receptors associated with tyrosine or serine/threonine kinase activities, proteins with seven transmembrane domains, or intracellular receptors.
View Article and Find Full Text PDFRewiring and optimization of metabolic networks to enable the production of commercially valuable chemicals is a central goal of metabolic engineering. This prospect is challenged by the complexity of metabolic networks, lack of complete knowledge of gene function(s), and the vast combinatorial genotype space that is available for exploration and optimization. Various approaches have thus been developed to aid in the efficient identification of genes that contribute to a variety of different phenotypes, allowing more rapid design and engineering of traits desired for industrial applications.
View Article and Find Full Text PDFRecombineering has been an essential tool for genetic engineering in microbes for many years and has enabled faster, more efficient engineering than previous techniques. There have been numerous studies that focus on improving recombineering efficiency, which can be divided into three main areas: (i) optimizing the oligo used for recombineering to enhance replication fork annealing and limit proofreading; (ii) mechanisms to modify the replisome itself, enabling an increased rate of annealing; and (iii) multiplexing recombineering targets and automation. These efforts have increased the efficiency of recombineering several hundred-fold.
View Article and Find Full Text PDFInfection around the shoulder joint is rare. Clinical suspicion and diagnostic imaging are required for accurate diagnosis. We present three cases that emphasise particular diagnostic challenges when dealing with infection around the shoulder joint.
View Article and Find Full Text PDFGlenohumeral septic arthritis is rare and usually a result of Staphylococcus aureus infection. Gram-negative septic arthritis is on the increase and is usually associated with intraabdominal pathology. We present a case of bilateral E.
View Article and Find Full Text PDFObjectives: The aim of this study was to characterize the antimicrobial profile of REP3123, a novel inhibitor of methionyl-tRNA synthetase (MetRS) in development for the treatment of Clostridium difficile infection.
Methods: The spectrum of activity of REP3123 was determined by susceptibility testing of C. difficile and non-target organisms.
Purpose: The Ras-Raf-mitogen-activated protein kinase kinase (MEK) pathway is overactive in many human cancers and is thus a target for novel therapeutics. We have developed a highly potent and selective inhibitor of MEK1/2. The purpose of these studies has been to show the biological efficacy of ARRY-142886 (AZD6244) in enzymatic, cellular, and animal models.
View Article and Find Full Text PDFJ Biomed Mater Res B Appl Biomater
October 2006
In an adult porcine model, the effectiveness of a bioresorbable film to minimize soft tissue attachment to the pelvic viscera was evaluated at 4-week and 12-week endpoints. Following a transperitoneal laparotomy through a midline incision, the bladder and uterus were abraded in all animals to promote soft tissue attachment to the viscera. Control animals received no further treatment.
View Article and Find Full Text PDFObjectives: An adult pig model of retrosternal adhesion formation via an inferior hemisternotomy was used to evaluate the formation and development of pericardial and retrosternal adhesions, as well as adhesion reduction using two thicknesses of a bioabsorbable polylactide film.
Materials And Methods: Twenty-five adult female pigs (70 kg) were allocated to either a control group or four different treatments using two thicknesses (0.02 or 0.
The reconstruction of a tendon-bone interface, as in rotator-cuff repairs, remains a challenging surgical problem. There is however, little data to show what effect joint position or repair loading under physiological conditions have on the repaired tendon-bone interface. A change in the amount of contact area or load at the tendon-bone interface may influence healing.
View Article and Find Full Text PDFClinical and research attention to stroke care has focused on managing the acute stage of recovery and on evaluating the short-term effectiveness of rehabilitation programs. However, studies suggest that stroke affects the quality of life and the well-being of the entire family over much longer time frames. This article reviews the stroke literature as it relates to stroke rehabilitation and the family.
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