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Nebulization of 2% lidocaine has no detectable impact on the healthy equine respiratory microbiota.
PLoS One
January 2025
Cummings School of Veterinary Medicine at Tufts University, Department of Infectious Diseases and Global Health, North Grafton, MA, United States of America.
Glucocorticosteroids remain the most common pharmaceutical approach for the treatment of equine asthma but can be associated with significant side effects, including respiratory microbiome alterations. The goal of the study was to assess the impact of 2% lidocaine nebulization, a projected alternative treatment of equine asthma, on the healthy equine respiratory microbiota. A prospective, randomized, controlled, blinded, 2-way crossover study was performed, to assess the effect of 1 mg/kg 2% lidocaine (7 treatments over 4 days) on the equine respiratory microbiota compared to control horses (saline and no treatment).
View Article and Find Full Text PDFStructure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.
Proc Natl Acad Sci U S A
January 2025
Cellular and Structural Physiology Laboratory, Advanced Research Initiative, Institute of Integrated Research, Institute of Science Tokyo, Bunkyo-ku, Tokyo 113-8510, Japan.
Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).
View Article and Find Full Text PDFAn alternatively translated isoform of PPARG proposes AF-1 domain inhibition as an insulin sensitization target.
Diabetes
January 2025
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
PPARγ is the pharmacological target of thiazolidinediones (TZDs), potent insulin sensitizers that prevent metabolic disease morbidity but are accompanied by side effects such as weight gain, in part due to non-physiological transcriptional agonism. Using high throughput genome engineering, we targeted nonsense mutations to every exon of PPARG, finding an ATG in Exon 2 (chr3:12381414, CCDS2609 c.A403) that functions as an alternative translational start site.
View Article and Find Full Text PDFProtective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.
FEBS J
January 2025
INSERM UMR-1100, "Research Center for Respiratory Diseases (CEPR)", Tours, France.
Transplanted organs are inevitably exposed to ischemia-reperfusion (IR) injury, which is known to cause graft dysfunction. Functional and structural changes that follow IR tissue injury are mediated by neutrophils through the production of oxygen-derived free radicals, as well as from degranulation which entails the release of proteases and other pro-inflammatory mediators. Neutrophil serine proteases (NSPs) are believed to be the principal triggers of post-ischemic reperfusion damage.
View Article and Find Full Text PDFGibberellin regulates the synthesis of stone cells in 'Nanguo' pear via the PuMYB91-PuERF023 module.
Physiol Plant
January 2025
Key Laboratory of Fruit Postharvest Biology, Liaoning Province; College of Horticulture, Shenyang Agricultural University, Shenyang, China.
Stone cells are one of the limiting factors affecting pear fruit quality and commodity value. The formation of stone cell is highly correlated with lignin deposition. However, the molecular mechanism of stone cell formation and regulation is still unclear.
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