A5053800389- Respiratory Support and Mechanisms
- Neonatal Respiratory Health Research
- Sepsis Diagnosis and Treatment
- Intensive Care Unit Cognitive Disorders
- Immune Response and Inflammation
- Air Quality and Health Impacts
- Thermal Regulation in Medicine
- Asthma and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Autophagy in Disease and Therapy
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Anesthesia and Neurotoxicity Research
- Immune cells in cancer
- COVID-19 Clinical Research Studies
- Mechanical Circulatory Support Devices
- Tracheal and airway disorders
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Heme Oxygenase-1 and Carbon Monoxide
- Cancer-related gene regulation
- Obstructive Sleep Apnea Research
- Metabolism, Diabetes, and Cancer
- Protein Kinase Regulation and GTPase Signaling
- Wireless Body Area Networks
- Advanced Sensor and Energy Harvesting Materials
The Ohio State University Wexner Medical Center
2016-2025
The Ohio State University
2018-2025
Accelerated Medical Diagnostics (United States)
2025
Lung Institute
2024-2025
Ochsner Health System
2025
University of Cincinnati
2024
King Saud University
2024
Cincinnati Children's Hospital Medical Center
2024
Ohio University
2023
University School
2021
Advancements in methods, technology, and our understanding of the pathobiology lung injury have created need to update definition experimental acute (ALI). We queried 50 participants with expertise ALI respiratory distress syndrome using a Delphi method composed series electronic surveys virtual workshop. propose that presents as “multidimensional entity” characterized by four “domains” reflect key pathophysiologic features underlying biology human syndrome. These domains are 1) histological...
Intestinal barrier dysfunction occurs following hemorrhagic shock and resuscitation (HS/R). High-mobility group B1 (HMGB1) has been shown to increase the permeability of Caco-2 human enterocyte-like epithelial monolayers in vitro. In this study, we found that serum concentrations HMGB1 were higher blood samples obtained from 25 trauma victims with than 9 normal volunteers. We also studied whether treatment anti-HMGB1 antibody can ameliorate HS/R-induced gut mice. Animals shocked by...
Macroautophagy is a highly conserved catabolic process that crucial for organ homeostasis in mammals. However, methods to directly measure macroautophagic activity (or flux) vivo are limited. In this study we developed quantitative flux assay based on measuring LC3b protein turnover after administering the protease inhibitor leupeptin. Using then characterized basal different mouse organs. We found rate of accumulation leupeptin treatment was greatest liver and lowest spleen. Interestingly...
Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS.We conducted phase I dose escalation trial to assess feasibility safety low-dose iCO administration patients sepsis-induced ARDS. Twelve participants were randomized or placebo air 2:1 two cohorts. Four subjects each administered (100 ppm cohort 1...
Acute respiratory distress syndrome (ARDS) represents a significant burden to the healthcare system, with ≈200 000 cases diagnosed annually in USA. ARDS patients suffer from severe refractory hypoxemia, alveolar-capillary barrier dysfunction, impaired surfactant function, and abnormal upregulation of inflammatory pathways that lead intensive care unit admission, prolonged hospitalization, increased disability-adjusted life years. Currently, there is no cure or FDA-approved therapy for ARDS....
Ethyl pyruvate has been shown to have anti-inflammatory properties in numerous cell culture and animal studies. In this series of experiments, we tested the hypothesis that ethyl inhibits signaling by pro-inflammatory transcription factor, NF-κB. inhibited luciferase expression lipopolysaccharide-stimulated murine macrophage-like RAW 264.7 cells transfected with an NF-κB-dependent reporter vector. also decreased NF-κB DNA-binding activity lipopolysaccharide-induced gene, inducible nitric...
Isoflurane may be protective in preclinical models of lung injury, but its use patients with injury remains controversial and the mechanism effects unclear. The authors hypothesized that this protection is mediated at level alveolar tight junctions investigated possibility a two-hit model mirrors human acute respiratory distress syndrome.Wild-type mice were treated isoflurane 1 h after exposure to nebulized endotoxin (n = 8) or saline control 9) then allowed recover for 24 before mechanical...
Abstract Mechanical ventilation generates injurious forces that exacerbate lung injury. These disrupt barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes non-coding oligonucleotides including microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages has therapeutic potential to mitigate injury during mechanical ventilation. We use humanized in-vitro systems, mouse models, biospecimens from patients...
The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe coronavirus 2) infection. Knowledge molecular mechanisms driving host responses to limited the lack reliable preclinical models that recapitulate human illness. Further, existing animal are not characterized as experimental lung injury (ALI) or ARDS. Acknowledging differences in and ARDS, here we systematically evaluate model result infection...
Abstract Sepsis remains the leading cause of death in critically ill patients, despite modern advances critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and development multiple organ syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated intestine sepsis, we hypothesized that it be maintenance intestinal epithelial function peritonitis-induced polymicrobial COX-2−/− COX-2+/+ BALB/c mice underwent cecal ligation puncture (CLP) or sham...
Mechanical ventilation is necessary to support patients with acute lung injury, but also exacerbates injury through mechanical stress-activated signaling pathways. We show that stretch applied cultured human cells, and mouse lungs in vivo, induces robust expression of metallothionein, a potent antioxidant cytoprotective molecule critical for cellular zinc homeostasis. Furthermore, genetic deficiency murine metallothionein genes exacerbated caused by high tidal volume ventilation, identifying...
The alveolar-capillary barrier is composed of epithelial and endothelial cells interacting across a fibrous extracelluar matrix (ECM). Although remodeling the ECM occurs during several lung disorders, it not known how fiber structure mechanics influences cell injury cyclic airway reopening as mechanical ventilation (atelectrauma). We have developed novel in vitro platform that mimics micro/nano-scale architecture alveolar microenvironment used this system to investigate microstructural...
In critical illness, such as sepsis or the acute respiratory distress syndrome, kidney injury (AKI) is common and associated with increased morbidity mortality. Mechanical ventilation in illnesses also a risk factor for AKI, but it potentially modifiable. Injurious strategies may lead to systemic release of inflammatory mediators from lung due ventilator induced (VILI). The consequences VILI are difficult differentiate clinically other syndromes, sepsis. purpose this study was identify...
Uncertainty persists whether anaerobic bacteria represent important pathogens in aspiration pneumonia. In a nested case-control study of mechanically ventilated patients classified as macro-aspiration pneumonia (MAsP, n = 56), non-macro-aspiration (NonMAsP, 91), and uninfected controls (n 11), we profiled upper (URT) lower respiratory tract (LRT) microbiota with bacterial 16S rRNA gene sequencing, measured plasma host-response biomarkers, analyzed communities by diversity oxygen...
Abstract Background The pathogenesis of asthma and airway obstruction is the result an abnormal response to different environmental exposures. scientific premise our study was based on finding that FoxO1 expression increased in lung macrophages mice after allergen exposure human asthmatic patients. Macrophages are capable switching from one functional phenotype another, it important understand mechanisms involved transformation how their cellular function affects peribronchial stromal...
Oxidative stress resulting from inflammatory responses that occur during acute lung injury and sepsis can initiate changes in mitochondrial function. Autophagy regulates cellular processes the setting of injury, sepsis, oxidative by modulating immune response facilitating turnover damaged components. We have shown mesenchymal stromal cells (MSCs) improve survival murine models also regulating response. However, effect autophagy on MSCs MSC function is unknown. This study investigated...
The pro-inflammatory response of alveolar macrophages to injurious physical forces during mechanical ventilation is regulated by the anti-inflammatory microRNA, miR-146a. Increasing miR-146a expression supraphysiologic levels using untargeted lipid nanoparticles reduces ventilator-induced lung injury but requires a high initial dose making it less clinically applicable. In this study, we developed mannosylated that can effectively mitigate at initiation with lower doses We used...
Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform of injured lungs generates complex forces that lead ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems simulate normal respiration, modeling the mechanics VILI as well subsequent recovery phase is a challenge. Here we present novel humanized
Checkpoint inhibitor pneumonitis (CIP) that develops following immune checkpoint (ICI) treatment can be difficult to distinguish from other common etiologies of lung inflammation in cancer patients. Here, we evaluate the bronchoalveolar lavage fluid (BAL) for potential biomarkers specific CIP. We conducted a retrospective study patients who underwent standard care bronchoscopy compare cytokines interest between with and without CIP immune-mediated pulmonary diseases. Pulmonary diagnoses were...