neutrophil substrate

Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl ( k  = 9.2 x 107 M-1 s-1 ), like glutathione ( k  = 1.2 x 108 M-1 s-1 ), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC50 =4...

The conversion of phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-triphosphate by phosphoinositide 3-kinase γ (PI3Kγ) is critical for neutrophil chemotaxis and cancer metastasis. PI3Kγ is activated by Gβγ heterodimers released from G protein-coupled receptors responding to extracellular signals. Here we determined cryo-electron microscopy structures of Sus scrofa PI3Kγ-human Gβγ complexes in the presence of substrates/analogs, revealing two Gβγ binding sites: one on the p110γ helical domain and another on the p101 C-terminal domain...

Neutrophil gelatinase-associated lipocalin (NGAL) is a remarkable biomarker for assessing acute kidney injury. In this study, we developed a novel label-free NGAL electrochemical immunosensor based on gold nanoparticles (AuNPs) and Prussian blue (PB) without an external mediator. The AuNPs-PB based immunosensor was fabricated on a custom gold-electrode (AuE)-based polypropylene (PP) substrate. We systematically assessed and optimized key experimental parameters, including the process of AuNPs-PB electrodeposition, antibody concentration, and incubation time...

Hydrolytic enzymes play crucial roles in cellular processes, and dysregulation of their activities is implicated in various physiological and pathological conditions. These enzymes cleave substrates such as peptide bonds, phosphodiester bonds, glycosidic bonds, and other esters. Detecting aberrant hydrolase activity is vital for understanding disease mechanisms and developing targeted therapeutic interventions. This study introduces a novel approach to measuring hydrolase activity using giant magnetoresistive (GMR) spin valve sensors...

There have been substantial advances in vascular protein disulfide isomerases (PDIs) in platelet function and thrombosis in recent years. There are 4 known prothrombotic thiol isomerases; PDI, endoplasmic reticulum protein (ERp)57, ERp72, and ERp46, and 1 antithrombotic PDI; transmembrane protein 1. A sixth PDI, ERp5, may exhibit either prothrombotic or antithrombotic properties in platelets. Studies on ERp46 in platelet function and thrombosis provide insight into the mechanisms by which these enzymes function...

Introduction: The development of bioconjugates for the targeted delivery of anticancer agents is gaining momentum after recent success of antibody drug conjugates (ADCs) in the clinic. Smaller format conjugates may have several advantages including better tumor penetration; however, cellular uptake and trafficking may be substantially different from ADCs. To fully leverage the potential of small molecule drug conjugates (SMDCs) with potent binding molecules mediating tumor homing, novel linker chemistries susceptible for efficient extracellular activation and payload release in the tumor microenvironment (TME) need to be explored...

Neutrophils play a dual role in protecting the body. They are able to penetrate infected tissues and destroy pathogens there by releasing aggressive bactericidal substances. While into the surrounding tissues, the aggressive products secreted by neutrophils initiate development of inflammatory processes. Invasion of neutrophils into tissues is observed during the development of pneumonia in the patients with lung diseases of various etiologies, including acute respiratory distress syndrome caused by coronavirus disease...

Study objectives were to compare the immune response, metabolism and production following intramammary lipopolysaccharide (IMM LPS) administration in early and mid-lactation cows. Early (E-LPS; n = 11; 20 ± 4 d in milk [DIM]) and mid- (M-LPS; n = 10; 155 ± 40 DIM) lactation cows were enrolled in an experiment consisting of 2 periods (P). During P1 (5 d) cows were fed ad libitum and baseline data were collected, including liver and muscle biopsies. At the beginning of P2 (3 d) cows received 10 mL sterile saline containing 10 µg of LPS from Escherichia coli O111:B4/mL into the left rear quarter of the mammary gland, and liver and muscle biopsies were collected at 12 h post-LPS...

Drug metabolism is an essential process that chemically alters xenobiotic substrates to activate or terminate drug activity. Myeloperoxidase (MPO) is a neutrophil-derived enzyme that is involved in killing invading pathogens, although consequentially, this same oxidative activity can produce metabolites that damage host tissue and play a role in various human pathologies. Cytochrome P450 (CYPs) are a superfamily of haem-containing enzymes that are majorly involved in the metabolism of drugs by functioning as monooxygenases and can be induced or inhibited, resulting in significant drug-drug interactions that lead to unanticipated adverse drug reactions...

Antibiotic resistance represents a significant challenge to public health and human safety. The primary driver behind the dissemination of antibiotic resistance is the horizontal transfer of plasmids. Current conjugative transfer assay is generally performed in a standardized manner, ignoring the effect of the host environment. Host defense peptides (HDPs) possess a wide range of biological targets and play an essential role in the innate immune system. Herein, we reveal that sub-minimum inhibitory concentrations of HDPs facilitate the conjugative transfer of RP4-7 plasmid in the Luria Broth medium, and this observation is reversed in the RPMI medium, designed to simulate the host environment...

Neutrophils are innate immune cells that respond quickly to sites of bacterial infection and play an essential role in host defense. Interestingly, some bacterial pathogens benefit from exuberant neutrophil inflammation. Salmonella is one such pathogen that can utilize the toxic mediators released by neutrophils to colonize the intestine and cause enterocolitis. Because neutrophils can aid gut colonization during Salmonella infection, neutrophils represent a potential host-directed therapeutic target. Myristoylated alanine-rich C-kinase substrate (MARCKS) is an actin-binding protein that plays an essential role in many neutrophil effector responses...

Inflammatory disease biomarker detection has become a high priority in point-of-care diagnostic research in relation to chronic wounds, with a variety of sensor-based designs becoming available. Herein, two primary aspects of biosensor design are examined: (1) assessment of a cellulose nanofiber (CNF) matrix derived from cotton ginning byproducts as a sensor transducer surface; and (2) assessment of the relation of spacer length and morphology between the CNF cellulose backbone and peptide fluorophore as a function of sensor activity for porcine pancreatic and human neutrophil elastases...

PURPOSE: Radiation induced pneumonitis (RIP) seriously limits the application of radiotherapy in the treatment of thoracic tumors, and its etiology and pathogenesis remain elusive. This study aims to elucidate the role of Ubiquitin-specific peptidase 11 (USP11) in the progression of RIP and the associated underlying mechanisms. METHODS AND MATERIALS: The changes of cytokines and infiltrated immune cells were detected by ELISA and IHC after exposed to 20 Gy X-ray with whole thorax irradiation...

BACKGROUND: Ferroptosis, an iron-dependent process that regulates cell death. Emerging evidences suggest that ferroptosis induces acute kidney injury (AKI) progression, and inhibiting ferroptosis provides an effect strategy for AKI treatment. The disruption of the NRF2-KEAP1 protein to protein interaction (PPI) induces NRF2 activation, which provides a promising strategy that can identify new ferroptosis inhibitors. A previous study revealed that tiliroside, a glycosidic flavonoid extracted from Edgeworthia chrysantha Lindl (buds), has anti-neuroinflammatory and neuroprotective effects via NRF2 activation...

BACKGROUND: The current studies demonstrate that SARS-CoV-2 infection results in increasing complications incidence and the total risk of death in cancer patients. SARS-CoV-2 infection triggers oxidative stress representing one of the major factors of the inflammation contributing to the complicated course of the diseases including cancer. AIM: To assess the effect of hypoxia caused by SARS-CoV-2 infection on the redox status of blood in patients with metastatic colorectal cancer (mCRC)...

Despite the importance of citrullination in physiology and disease, global identification of citrullinated proteins, and the precise targeted sites, has remained challenging. Here we employed quantitative-mass-spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites within the HL60 leukemia cell line following differentiation into neutrophil-like cells. We identified 14,056 citrullination sites within 4,008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4...

Netherton syndrome (NS) is a rare skin disease caused by loss-of-function mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) gene. Disease severity and the lack of efficacious treatments call for a better understanding of NS mechanisms. Here we describe a novel and viable, Spink5 conditional knock-out (cKO) mouse model, allowing to study NS progression. By combining transcriptomics and proteomics, we determine a disease molecular profile common to mouse models and NS patients. Spink5 cKO mice and NS patients share skin barrier and inflammation signatures defined by up-regulation and increased activity of proteases, IL-17, IL-36, and IL-20 family cytokine signaling...

Every 1.2 s, a diabetic foot ulcer is developed, and every 20 s, one amputation is carried out in diabetic patients. Monitoring and controlling protease activity have been considered as a strategy for more efficient management of diabetic and other chronic wounds. This study aimed to develop a casein-based dressing that, by its disappearance, provides information about the activity of proteases and simultaneously harnesses proteolytic activity. Casein films were fabricated by using an aqueous solution, and heat treatment was successfully deployed as a green and clean approach to confer hydrolytic stability...

SIGNIFICANCE: Neutrophils are crucial components of the innate immune system that combat invading pathogens and maintain homeostasis. Nitric oxide (NO•) exerts regulatory influence on neutrophil rolling, adhesion, oxidative burst, chemotaxis, phagocytosis, cytoneme, apoptosis, and NETosis by diverse mechanisms in autocrine and paracrine manner. RECENT ADVANCES: Recent research has identified the critical role of NO• in the proliferation of neutrophil progenitors, differentiation, survival, and other functions...

BACKGROUND: Heparins are sulfated glycosaminoglycans that are used as anticoagulants to treat thrombosis. Heparins exhibit other potential therapeutic effects, such as anti-inflammatory, anti-viral, and anti-malarial effects. However, the strong anticoagulant activity of heparins poses a risk of life-threatening bleeding, limiting their therapeutic use for other diseases beyond thrombosis. To exploit the other effects of heparins and eliminate the bleeding risk, we explored an alternative polymer called lignosulfonic acid sodium (LSAS), which acts as a sulfonated heparin mimetic...