A5063483736- Inflammatory mediators and NSAID effects
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Neuroinflammation and Neurodegeneration Mechanisms
- Estrogen and related hormone effects
- Epilepsy research and treatment
- Ion channel regulation and function
- Peptidase Inhibition and Analysis
- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Adenosine and Purinergic Signaling
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Neuropeptides and Animal Physiology
- Ion Channels and Receptors
- Immune Response and Inflammation
- Cancer, Stress, Anesthesia, and Immune Response
- Nitric Oxide and Endothelin Effects
- Drug Transport and Resistance Mechanisms
- Genetics and Neurodevelopmental Disorders
- Hippo pathway signaling and YAP/TAZ
- Cancer therapeutics and mechanisms
- Autophagy in Disease and Therapy
- interferon and immune responses
University of Tennessee Health Science Center
2019-2025
University of Cincinnati Medical Center
2014-2023
Hangzhou First People's Hospital
2022
Emory University
2012-2015
University of Cincinnati
2015
Ajou University
2015
Auburn University
2005-2008
Cotton Research Institute
2004
Nanjing Agricultural University
2004
East China University of Science and Technology
2000
Prostaglandin E2 is now widely recognized to play critical roles in brain inflammation and injury, although the responsible prostaglandin receptors have not been fully identified. We developed a potent selective antagonist for receptor subtype EP2, TG6-10-1, with sufficient pharmacokinetic profile be used vivo. found that mouse pilocarpine model of status epilepticus (SE), systemic administration TG6-10-1 completely recapitulates effects conditional ablation cyclooxygenase-2 from principal...
See Ghoshal and Claassen (doi:10.1093/brain/awx226) for a scientific commentary on this article. Early cortical infarcts are common in poor-grade patients after aneurysmal subarachnoid haemorrhage. There no animal models of these lesions mechanisms unknown, although mass spreading depolarizations hypothesized as requisite mechanism clinical marker infarct development. Here we studied acute sequelae haemorrhage the gyrencephalic brain propofol-anaesthetized juvenile swine using subdural...
Protein aggregates can form in the cytoplasm of cell and are accumulated at aggresomes localized to microtubule organizing center (MTOC) where they subsequently degraded by autophagy. In this process, engulfed into autophagosomes which fuse with lysosomes for protein degradation. A member class II histone deacetylase family, 6(HDAC6) has been shown be involved both aggresome formation fusion making it an attractive target regulate aggregation. The scaffolding sequestosome 1(SQSTM1)/p62 also...
With interest waning in the use of cyclooxygenase-2 (COX-2) inhibitors for inflammatory disease, prostaglandin receptors provide alternative targets treatment COX-2–mediated pathological conditions both periphery and central nervous system. Activation E2 receptor (PGE 2 ) subtype EP2 promotes inflammation is just beginning to be explored as a therapeutic target. To better understand physiological functions receptor, we developed suite small molecules with 3-aryl-acrylamide scaffold selective...
Population studies, preclinical, and clinical trials suggest a role for cyclooxygenase-2 (COX-2, <i>PTGS2</i>) in tumor formation progression. The downstream prostanoid receptor signaling pathways involved tumorigenesis are poorly understood, although prostaglandin E2 (PGE<sub>2</sub>), major COX-2 metabolite which is usually upregulated the tissues, presumably plays important roles biology. Taking advantage of our recently identified novel selective antagonist EP2 (<i>PTGER2</i>) subtype...
Activation of EP2 receptors by prostaglandin E2 (PGE2) promotes brain inflammation in neurodegenerative diseases, but the pathways responsible are unclear. couple to Gαs and increase cAMP, which associates with protein kinase A (PKA) cAMP-regulated guanine nucleotide exchange factors (Epacs). Here, we studied function its signaling rat microglia their resting state or undergoing classical activation vitro following treatment low concentrations lipopolysaccharide interferon-γ. Real time PCR...
Activation of the Gαs-coupled EP2 receptor for prostaglandin E2 (PGE 2 ) promotes cell survival in several models tissue damage. To advance understanding functions, we designed experiments to develop allosteric potentiators this key receptor. Screens 292,000 compounds identified 93 that at 20 μM ( i potentiated cAMP response a low concentration PGE by > 50%; ii had no effect on EP4 or β2 adrenergic receptors, assay itself, parent line; and iii increased potency receptors least 3-fold. In...
Cyclooxygenase-2 (COX-2) triggers pro-inflammatory processes that can aggravate neuronal degeneration and functional impairments in many neurological conditions, mainly via producing prostaglandin E2 (PGE2) activates four membrane receptors, EP1-EP4. However, which EP receptor is the culprit of COX-2/PGE2-mediated inflammation remains largely unclear presumably depends on insult types responding components. Herein, we demonstrated COX-2 was induced showed nuclear translocation two cell lines...
Background and Purpose An up‐regulation of COX‐2 in malignant gliomas causes excessive synthesis PGE 2 , which is thought to facilitate brain tumour growth invasion. However, downstream receptor subtype (i.e., EP 1 –EP 4 ) directly contributes COX activity‐promoted glioma remains largely unknown. Experimental Approach Using a publicly available database from The Cancer Genome Atlas research network, we compared the expression signalling‐associated genes human lower grade glioblastoma...
Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in variety of central nervous system and peripheral diseases. A highly selective antagonist could be useful as drug to mitigate the inflammatory consequences activation. We recently identified cinnamic amide class antagonists. The lead compound this (5d) displays anti-inflammatory neuroprotective actions. However, exhibited moderate selectivity over DP1 prostanoid (∼10-fold) low aqueous solubility. now...
The timely resolution of inflammation prevents continued tissue damage after an initial insult. In the brain, death activated microglia by apoptosis has been proposed as one mechanism to resolve brain inflammation. How microglial is regulated activation still unclear. We reported that exposure lipopolysaccharide (LPS) and interleukin (IL)-13 together initially activates then kills rat in culture a dependent on cyclooxygenase-2 (COX-2). show here E prostanoid receptor 2 (EP2, PTGER2) for...
Abstract Objective The objective of this study was to identify the signaling pathway that is immediately triggered by status epilepticus (SE) and in turn contributes excessive brain‐derived neurotrophic factor (BDNF)/tropomyosin‐related kinase receptor B (TrkB) within hippocampus. Methods We used quantitative PCR, enzyme‐linked immunosorbent assay, Western blot analysis examine gene expression at both mRNA protein levels hippocampus following prolonged SE mice rats. Three classical animal...