Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, () is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards LPS and was bactericidal against MDR derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR infections, especially in the presence of BPI-ANCA.
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http://dx.doi.org/10.7554/eLife.86369 | DOI Listing |
Differentiation
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China. Electronic address:
Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints.
View Article and Find Full Text PDFBioorg Chem
December 2024
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address:
Enhancer of Zeste Homolog 2 (EZH2) is overexpressed in many malignancies and plays a critical role in cancer progression. Therefore, it is considered a promising target for therapeutic intervention. Although several EZH2 inhibitors have entered clinical trials, only one has received FDA approval.
View Article and Find Full Text PDFJ Fluoresc
December 2024
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
A simple and highly effective Schiff-base fluorescent chemosensor (S1) was synthesized and characterized by HNMR and fluorescence spectroscopy. The synthesized chemosensor was applied for the selective and sensitive detection of Hg ions. The chemosensor exhibited a strong 'turn-on' fluorescence response in a CHOH/HO (1:9, v/v) solution due to complex formation (S1-Hg) which block photo induce electron transfer (PET).
View Article and Find Full Text PDFAddict Sci Clin Pract
December 2024
University of Connecticut School of Medicine, Farmington, CT, 06032, USA.
Background: Contingency management (CM), an incentive-based intervention to encourage target behaviors, effectively promotes medication adherence. However, efforts to extend CM to HIV pre-exposure prophylaxis (PrEP) have been lacking. As part of a randomized clinical trial to promote HIV Prevention among people who inject drugs (PWID), we examined the readiness of staff in community-based organizations serving PWID to implement CM for PrEP uptake and adherence in this population.
View Article and Find Full Text PDFSkelet Muscle
December 2024
School of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Background: Muscle stem cells (MuSCs) undergo numerous state transitions throughout life, which are critical for supporting normal muscle growth and regeneration. Epigenetic modifications in skeletal muscle play a significant role in influencing the niche and cellular states of MuSCs. Mixed-lineage leukemia 4 (Mll4) is a histone methyltransferase critical for activating the transcription of various target genes and is highly expressed in skeletal muscle.
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