A5084194555- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Cancer-related molecular mechanisms research
- Inflammasome and immune disorders
- Extracellular vesicles in disease
- Sepsis Diagnosis and Treatment
- Signaling Pathways in Disease
- MicroRNA in disease regulation
- Advanced Nanomaterials in Catalysis
- Caveolin-1 and cellular processes
- Nanowire Synthesis and Applications
- Peptidase Inhibition and Analysis
- Neonatal and Maternal Infections
- Streptococcal Infections and Treatments
- Thermal Regulation in Medicine
- Antimicrobial Peptides and Activities
- Adenosine and Purinergic Signaling
- Cardiac Ischemia and Reperfusion
- Mechanical Circulatory Support Devices
- RNA modifications and cancer
- Inflammation biomarkers and pathways
- Circular RNAs in diseases
- Nanoplatforms for cancer theranostics
University of Michigan
2018-2024
Xiangya Hospital Central South University
2018-2023
Central South University
2016-2023
Michigan Medicine
2020-2021
Arbor Research Collaborative for Health
2020
Michigan United
2019
The MTOC is “speck”-tacular Inflammasome complexes are formed in response to pathogen-associated molecules. They initiate both the maturation of inflammatory cytokines and pyroptosis, a type programmed cell death. One notable feature for inflammasome activation formation single supramolecular punctum (or “speck”) each affected cell. However, location mechanism speck poorly understood. Magupalli et al. report that NLRP3- pyrin-mediated inflammasomes, their assembly downstream functions occur...
Sepsis results in millions of deaths every year, with acute lung injury (ALI) being one the leading causes mortality septic patients. As neutrophil extracellular traps (NETs) are abundant sepsis, neutralizing components NETs may be a useful strategy to improve outcomes sepsis. Citrullinated histone H3 (CitH3) has been recently shown involved NET formation. In this study, we demonstrate that CitH3 damages human umbilical vein endothelial cells (HUVECs) and potentiates formation through...
Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes that involved in variety human disorders, including cancer and autoimmune diseases. Although targeting PAD4 has shown no benefit sepsis, the role PAD2 remains unknown. Here, we report is engaged sepsis sepsis-induced acute lung injury both patients mice. Pad2–/– or selective inhibition by small molecule inhibitor increased survival improved overall outcomes mouse models sepsis. Pad2 deficiency decreased neutrophil...
Abstract Purpose Microbial infection stimulates neutrophil/macrophage/monocyte extracellular trap formation, which leads to the release of citrullinated histone H3 (CitH3) catalyzed by peptidylarginine deiminase (PAD) 2 and 4. Understanding these molecular mechanisms in pathogenesis septic shock will be an important next step for developing novel diagnostic treatment modalities. We sought determine expression CitH3 patients with shock, correlate levels PAD2/PAD4 clinically relevant outcomes....
Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood whether how post-translational modifications (PTMs) intrinsically affect the phenotype function of TAMs. Here, we reveal that peptidylarginine deiminase 4 (PAD4) exhibits highest expression among common PTM enzymes in TAMs negatively correlates with clinical response to immune checkpoint blockade. Genetic pharmacological inhibition PAD4 prevents progression tumor-bearing mouse...
BACKGROUND Early single-dose treatment with human mesenchymal stem cell–derived exosomes promotes neuroprotection and blood-brain barrier integrity in models of traumatic brain injury (TBI) hemorrhagic shock (HS) swine. The impact an early single dose on late survival (7 days), however, remains unknown. We sought to evaluate the exosome neurologic outcomes, lesion size, inflammatory cytokines, apoptotic markers, mediators neural plasticity a 7-day model. METHODS Yorkshire swine were...
Abstract Bacterial infections leading to sepsis are a major cause of deaths in the intensive care unit. Unfortunately, no effective methods available capture early onset infectious near patient with both speed and sensitivity required for timely clinical treatment. To fill gap, authors develop highly miniaturized (2.5 × 2.5 µm 2 ) plasmo‐photoelectronic nanostructure device that detected citrullinated histone H3 (CitH3), biomarker released blood circulatory system by neutrophils. Rapidly...
We have shown that administration of mesenchymal stem cell-derived exosomes (single dose given within 1 hour) in models traumatic brain injury (TBI) and hemorrhagic shock is neuroprotective. The precise mechanisms responsible for the neuroprotection are not fully understood. This study was designed to investigate transcriptomic changes associated with this treatment strategy.Yorkshire swine (40-45 kg) were subjected a severe TBI (12-mm cortical impact) (40% estimated total blood volume). One...
Abstract Background Pseudomonas aeruginosa (PA) is a pathogenic bacterium that causes severe pneumonia in critically ill and immunocompromised patients. Peptidylarginine deiminase (PAD) 2, PAD4, caspase-1 are important enzymes mediating host response to infection. The goal of this study was determine the interplay between PAD2, PA pneumonia-induced sepsis. Methods Pneumonia produced wild-type, Pad2−/−, Pad4−/− mice by intranasal inoculation (2.5 × 106 colony-forming units per mouse),...
Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection that often results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). An emerging mechanism of sepsis-induced ARDS involves neutrophils/macrophages undergoing cell death, releasing nuclear histones cause tissue damage exacerbates pulmonary injury. While published studies focus on unmodified histones, little known about the role citrullinated histone H3 (CitH3) pathogenesis...
Objective: Sepsis causes millions of deaths on a global scale annually. Activation peptidylarginine deiminase (PAD) enzymes in sepsis citrullination histones, which results neutrophil extracellular trap formation and progression. This study evaluates pan-PAD inhibitor, Cl-amidine, model lipopolysaccharide (LPS)-induced endotoxic shock rabbits. We hypothesized that Cl-amidine would improve survival attenuate kidney injury. Methods: In the model, rabbits were injected intravenously with 1...
Background: Histone deacetylase (HDAC) 6 inhibitors have demonstrated significant protective effects in traumatic injuries. However, their roles neuroprotection and underlying mechanisms are poorly understood. This study sought to investigate the neuroprotective of Tubastatin A (Tub-A), an HDAC6 inhibitor, during oxygenglucose deprivation (OGD) HT22 hippocampal cells. Methods: cells were exposed OGD. Cell viability cytotoxicity assessed by cell counting kit-8 (CCK-8) lactate dehydrogenase...
ABSTRACT Background: The peptidylarginine deiminase (PAD) family converts arginine into citrulline through protein citrullination. PAD2 and PAD4 inhibitors can improve survival in hemorrhagic shock (HS). However, the impact of isoform-specific PAD inhibition improving has not been studied. In this study, we utilize selective Pad2 −/− knockout mice to elucidate loss function leads pro-survival effect HS. Methods: HS : wild-type (WT) (n = 5/group) were subjected lethal (55% volume hemorrhage)....
Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management non-compressible torso hemorrhage has been at forefront trauma care recent years. Since complete aortic occlusion presents serious concerns, concept partial gained a growing attention. Here, we present large animal model hemorrhagic shock to investigate effects novel balloon catheter and compare it with that works on principles occlusion. Swine are anesthetized instrumented order conduct controlled...
In article number 1905611, Yongqing Li, Xiaogan Liang, Katsuo Kurabayashi, and co-workers describe a highly miniaturized plasmo-photoelectronic device incorporating high-affinity antibody-conjugated structurally engineered hemispherical gold nanoparticles molybdenum disulfide photoconductive channel to detect blood biomarker released by neutrophils at the early onset of bacterial infections.