() is an opportunistic pathogen naturally resistant to many common antibiotics and acquires new resistance traits at an alarming pace. Targeting the bacterial virulence factors by an antivirulence strategy, therefore, represents a promising alternative approach besides antibiotic therapy. The Type III secretion system (T3SS) of is one of its main virulence factors. It consists of more than 20 proteins building a complex syringe-like machinery enabling the injection of toxin into host cells. Previous works showed that disrupting interactions between components of this machinery efficiently lowers the bacterial virulence. Using automated target-based screening of commercial and in-house libraries of small molecules, we identified compounds inhibiting the protein-protein interaction between PscE and PscG, the two cognate chaperones of the needle subunit PscF of T3SS. Two hits were selected and assembled using Split/Mix/Click chemistry to build larger hybrid analogues. Their efficacy and toxicity were evaluated using phenotypic analysis including automated microscopy and image analysis. Two nontoxic hybrid leads specifically inhibited the T3SS and reduced the cytotoxicity of bacteria and their virulence in .
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http://dx.doi.org/10.1021/acsinfecdis.9b00154 | DOI Listing |
Front Biosci (Landmark Ed)
January 2025
Department of Neurology, Jinshan Hospital, Fudan University, 201508 Shanghai, China.
Background: Neuronal cholesterol deficiency may contribute to the synaptopathy observed in Alzheimer's disease (AD). However, the underlying mechanisms remain poorly understood. Intact synaptic vesicle (SV) mobility is crucial for normal synaptic function, whereas disrupted SV mobility can trigger the synaptopathy associated with AD.
View Article and Find Full Text PDFViruses
December 2024
Thomas H. Gosnell School for Life Sciences, Rochester Institute of Technology, Rochester, NY 14623, USA.
Vesicular Stomatitis Virus (VSV) has emerged as a promising candidate for various clinical applications, including vaccine development, virus pseudotyping, and gene delivery. Its broad host range, ease of propagation, and lack of pre-existing immunity in humans make it ideal for therapeutic use. VSV's potential as an oncolytic virus has garnered attention; however, resistance to VSV-mediated oncolysis has been observed in some cell lines and tumor types, limiting its effectiveness.
View Article and Find Full Text PDFNutrients
January 2025
Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Yanpu Township 90741, Taiwan.
: This study investigated the wound-healing potential of hispolon, a polyphenolic pigment derived from medicinal mushrooms, under diabetic conditions using both in vitro and in vivo models. : In the in vitro assays, L929 fibroblast cells exposed to high glucose (33 mmol/L) were treated with hispolon at concentrations of 2.5, 5, 7.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department XI Pediatrics, Discipline I Pediatrics, 'Victor Babeș' University of Medicine and Pharmacy of Timișoara, 300041 Timișoara, Romania.
The prevalence of goiter, thyroid nodules, and thyroid cancers in the pediatric population has increased. In some rare cases, local conditions such as juvenile desmoid-type fibromatosis (JDTF) can mimic specific thyroid pathology, complicating the diagnostic process. A 17-year-old obese adolescent girl was admitted to the Endocrinology Department with progressive swelling on the left side of the neck, persisting for approximately one year, recently accompanied by dysphonia and inspiratory dyspnea, and ultimately diagnosed as a unilateral nodular goiter associated with compressive phenomena.
View Article and Find Full Text PDFJ Clin Med
January 2025
Miguel Servet University Hospital, Avenida Isabel la Católica 1-3, 50009 Zaragoza, Aragón, Spain.
: Type 1 diabetes mellitus (T1DM) in pediatric patients often leads to emotional distress, impacting self-management. The PAID-Peds survey measures diabetes-related emotional burden but lacks a validated Spanish version. This study aimed to validate the Spanish PAID-Peds survey in children and adolescents with T1DM and correlate it with diabetic metabolic control parameters.
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