A5020551138- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Photoacoustic and Ultrasonic Imaging
- Mitochondrial Function and Pathology
- Cardiac Arrest and Resuscitation
- Neuroinflammation and Neurodegeneration Mechanisms
- Glycosylation and Glycoproteins Research
- Thermal Regulation in Medicine
- Optical Imaging and Spectroscopy Techniques
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Thermography and Photoacoustic Techniques
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Cardiac Ischemia and Reperfusion
- RNA modifications and cancer
- Neurological Disease Mechanisms and Treatments
- Cancer-related Molecular Pathways
- Biochemical effects in animals
- Photoreceptor and optogenetics research
- Genetic Neurodegenerative Diseases
- Nanoplatforms for cancer theranostics
- Anesthesia and Neurotoxicity Research
- Acute Ischemic Stroke Management
Duke University Hospital
2016-2025
Duke Medical Center
2016-2025
Duke University
2016-2025
Chongqing Medical University
2022-2025
Longgang Central Hospital
2025
Tongji Hospital
2022
Hong Kong Baptist University
2022
Capital University
2022
Capital Medical University
2022
California University of Pennsylvania
2022
Ischemic stroke is a medical emergency that primarily affects the elderly. A complex immune response in post-stroke brain constitutes key component of pathophysiology. This study aimed to determine how cell populations aged based on molecular profiles individual cells.
Small ubiquitin-like modifier (SUMO)2/3 but not SUMO1 conjugation is activated after transient cerebral ischemia. To investigate its function, we blocked neuronal SUMO2/3 translation through lentiviral microRNA delivery in primary cortical neurons. Viability was unaffected by silencing unless neurons were stressed oxygen–glucose deprivation (OGD). Both 15 and 45 minutes of OGD tolerated control microRNA-expressing damaged >60% expressing microRNA. Damaging (75 minutes) increased loss to...
Optical-resolution photoacoustic microscopy (OR-PAM) has become a popular tool in small-animal hemodynamic studies. However, previous OR-PAM techniques variously lacked high imaging speed and/or large field of view, impeding the study highly dynamic physiologic and pathophysiologic processes over region interest. Here we report high-speed system with an ultra-wide enabled by innovative water-immersible hexagon-mirror scanner. By driving scanner high-precision DC motor, new achieved...
Impaired function of the endoplasmic reticulum (ER stress) is a hallmark many human diseases including stroke. To restore ER in stressed cells, unfolded protein response (UPR) induced, which activates 3 stress sensor proteins activating transcription factor 6 (ATF6). ATF6 then cleaved by proteases to form short-form (sATF6), factor. determine extent activation UPR branch defines fate and neurons after stroke, we generated conditional tamoxifen-inducible sATF6 knock-in mouse. express...
Background and Purpose— Ischemic stroke impairs endoplasmic reticulum (ER) function, causes ER stress, activates the unfolded protein response. The response consists of 3 branches controlled by stress sensor proteins, which include PERK (protein kinase RNA-like kinase). Activated phosphorylates eIF2α (eukaryotic initiation factor 2 alpha), resulting in inhibition global synthesis. Here, we aimed to clarify role branch stroke. Methods— Neuron-specific tamoxifen-inducible conditional knockout...
A new group of proteins, small ubiquitin-like modifier (SUMO) has recently been identified and protein sumoylation shown to play a major role in various signal transduction pathways. Here, we report that transient global cerebral ischemia induces marked increase sumoylation. Mice were subjected 10 mins severe forebrain followed by 3 or 6 h reperfusion. Transient induced massive SUMO2/3 both the hippocampus cortex. conjugation was associated with decrease levels free SUMO2/3. After ischemia,...
Current available therapies for neonatal hypoxia/ischemia (H/I) brain injury are rather limited. Here, we investigated the effect of omega-3 polyunsaturated fatty acids on damage and long-term neurological function after H/I in neonates.Female rats were treated with or without an acids-enriched diet from second day pregnancy until 14 days parturition. Seven-day-old neonates subjected to euthanized 5 weeks later evaluation tissue loss. Neurological impairment was assessed progressively by...
This study was designed to investigate whether small ubiquitin-like modifier (SUMO) conjugation is activated after focal cerebral ischemia. Transient ischemia induced a dramatic increase in SUMO2/3 protein conjugates. The most pronounced changes were found the parietal cortex. particularly high neurons located at border of middle artery territory where sumoylated proteins translocated nucleus. Considering marked effect SUMO on function target proteins, it very likely that postischemic...
Small ubiquitin-like modifier (SUMO) conjugation is a post-translational modification associated with many human diseases. Characterization of the SUMO-modified proteome pivotal to define mechanistic link between SUMO and such This particularly evident for SUMO2/3 conjugation, which massively activated after brain ischemia/stroke, believed be protective response. The purpose this study was perform comprehensive analysis SUMO3-modified regulated by ischemia using novel transgenic mouse.To...
Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of variety age-related brain diseases including stroke. To restore function impaired stress, the unfolded response activated. A prosurvival pathway controlled stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification proteins (O-GlcNAcylation). Stroke impairs function, which activates response. The rationale this...
Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving outcomes, yet none succeeded clinical setting. This lack of success is largely due to our incomplete understanding how cells respond stroke. The objective current study was dissect effect permanent on microglia, resident within brain parenchyma. A middle cerebral artery occlusion (pMCAO) model used induce ischemic young male female mice. Microglia...
Transient cerebral ischemia dramatically activates small ubiquitin-like modifier (SUMO2/3) conjugation. In cells exposed to 6 h of transient oxygen/glucose deprivation (OGD), a model ischemia, SUMOylation increases profoundly between 0 and 30 min following re-oxygenation. To elucidate the effect OGD on SUMO conjugation target proteins, we neuroblastoma B35 expressing HA-SUMO3 used stable isotope labeling with amino acids in cell culture (SILAC) quantify OGD-induced changes levels specific...
Optical-resolution photoacoustic microscopy (OR-PAM) can provide functional, anatomical, and molecular images at micrometer level resolution with an imaging depth of less than 1 mm in tissue. However, the speed traditional OR-PAM is often low due to point-by-point mechanical scanning cannot capture time-sensitive dynamic information. In this work, we demonstrate a recent effort improving OR-PAM, using newly developed water-immersible two-axis scanner. Driven by water-compatible...
Many pathologic states can lead to the accumulation of unfolded/misfolded proteins in cells. This causes endoplasmic reticulum (ER) stress and triggers unfolded protein response (UPR), which encompasses three main adaptive branches. One these UPR branches is mediated by kinase RNA-like ER (PERK), an sensor. The primary consequence PERK activation suppression global synthesis, reduces workload facilitates recovery function. Ischemic stroke induces activates UPR. Studies have demonstrated...
Small ubiquitin-like modifier (SUMO1-3) constitutes a group of proteins that conjugate to lysine residues target thereby modifying their activity, stability, and subcellular localization. A large number SUMO are transcription factors other nuclear involved in gene expression. Furthermore, conjugation plays key roles genome quality control newly synthesized proteins, proteasomal degradation DNA damage repair. Any marked increase levels SUMO-conjugated is therefore expected have major impact...
To evaluate the effect of age on response brains to an ischemic challenge, we subjected young and aged mice transient forebrain ischemia, analyzed heat shock unfolded protein response, ubiquitin conjugation SUMO conjugation, O-linked β-N-acetylglucosamine modification proteins (O-GlcNAcylation). The most prominent age-related difference was inability activate O-GlcNAcylation. Considering many reports protective role O-GlcNAcylation in various stress conditions including myocardial this...
Abstract Background Cardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation re-established. This dire situation partly due to post-CA syndrome for which no specific effective intervention available. One key component of sterile inflammation, affects various organs including the brain. A major effector inflammation activated NLRP3 inflammasome, leads increased release interleukin (IL)-1β. However, how inflammasome impacts neuroinflammation...