Ischemic heart disease (IHD) is the leading cause of death, with age range being primary factor for development. The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. We aim use single-cell RNA sequencing discover transcriptional differences in various cell types between aged and young mice, may contribute aged-related insult. Utilizing 10× Genomics Single-Cell sequencing, we were able complete bioinformatic analysis identity novel differential...

More than 75% of traumatic brain injuries (TBIs) are mild (mTBI) and military service members often experience repeated combat-related mTBI. The chronic comorbidities concomitant with repetitive mTBI (rmTBI) include depression, post-traumatic stress disorder or neurological dysfunction. This study sought to determine a long noncoding RNA (lncRNA) expression signature in serum samples that correlated rmTBI years after the incidences. Serum were obtained from Long-Term Impact Military-Relevant...

Wound healing progresses through four phases: hemostasis, inflammation, proliferation, and remodeling. Wounds may become chronic if this process is disrupted. The use of small extracellular vesicle (sEV; EVs < 200 nm) exosomes (exo; ~40–120 derived from human adipose stem cells (hASCs) as a treatment for wounds well studied. cargo these great interest accelerates wound healing. Our previous studies identified lncRNAs GAS5 MALAT1 packaged enriched in hASC exosomes. In study, we rat model...

In the United States, an estimated 38 million individuals (10% of population) have type 2 diabetes mellitus (T2D), while approximately 97.6 adults (38%) prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators gene expression and metabolism. We were first to demonstrate that lncRNA Growth Arrest-Specific Transcript 5 (GAS5 (human)/gas5 (mouse)) is decreased in serum T2D patients established GAS5 as a biomarker for diagnosis onset prediction, now validated by other groups. further...

A progressive defect in the energy generation pathway is implicated multiple aging-related diseases, including cardiovascular conditions and Alzheimer's Disease (AD). However, evidence of pathogenesis cardiac dysfunction AD associations between two organ diseases need further elucidation. This study aims to characterize cellular defects resulting decreased function AD-model. 5XFAD mice, a strain expressing five mutations human APP PS1 that shows robust Aβ production with visible plaques at 2...

Elderly patients (age > 75) sustain larger infarcts with greater mortality from ST elevation myocardial (STEMI) despite successful reperfusion treatment. age remains an independent risk correction for clinical and angiographic variables. The elderly represent a high-risk population may benefit treatment in addition to alone. We hypothesized that modulation of cardiac signaling metabolism acute, high dose metformin given at would exhibit additional cardioprotection. Using translational aging...

Obesity is of concern to the population because it known cause inflammation and oxidative stress throughout body, leading patient predisposition for health conditions such as diabetes, hypertension, some cancers. However, proteins that are activated in times may provide cytoprotective properties. In this study, we aim gain further understanding interconnection between Nrf2 Sesn2 during obesity-related how relationship can play a role cardio-protection. Cardiomyocyte-specific knockout...

Whereas adrenergic stimulation promotes cardiac function that demands more fuel and energy, how this receptor controls glucose metabolism is not defined. This study shows the β2 adrenoreceptor (β2AR) required to increase transporter 4 (GLUT4)-mediated uptake in myocytes oxidation working hearts via activating β2AR G inhibitory-phosphoinositide 3-kinase-protein kinase B cascade phosphorylation of TBC1D4 (aka AS160), a Rab guanosine triphosphatase-activating protein, which key enzyme mobilize...

Acute kidney injury (AKI) leads to acute cardiac and dysfunction in cardiorenal syndrome Type 3 (CRS3) through oxidative stress (OS). The stress-inducible Sestrin2 (Sesn2) protein reduces reactive oxygen species (ROS) accumulation activates AMP-dependent kinase (AMPK) regulate cellular metabolism energetics during OS. Sesn2 levels its protective effects decline the aged heart. Antidiabetic drug metformin upregulates response ischemia–reperfusion (IR) stress. However, role of CRS3 remains...

Epilepsy is one of the most common and oldest neurological disorders, characterized by periodic seizures that affect millions globally. Despite its long history, pathophysiology not fully understood. Additionally, current treatment methods have their limitations. Finding a new alternative necessary. Activated Protein C (APC) has been proven to protection in other disorders; however, there no study focuses on role APC seizures. We propose APC's protective effect could be associated with...

Abstract Disclosure: M.A. Krause-Hauch: None. R. Patel: B. Osborne: P. Albear: N.A. Many patients struggle with chronic recalcitrant wounds that are the result of delayed healing. Underlying inflammation is one major risk factor for impaired dermal wound healing may lead to pathologies such as infection and scarring. Adult human adipose stem cells (hASCs) have shown tremendous potential in regenerative medicine. The hASCs dependent on secreted bioactive material which packaged released...

Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKCδI is a serine/threonine kinase which regulates cell growth, differentiation, survival. Caspase-3 cleavage of releases the C-terminal catalytic fragment (PKCδI_C), inflammation apoptosis. We previously demonstrated an increase in PKCδI_C human obese adipose tissue (AT) adipocytes. Subsequently, we designed small molecule drug called NP627 that specifically inhibited release vitro. Here, evaluate vivo...

Type 2 diabetes mellitus is a chronic metabolic disease with no cure. Adipose tissue major site of systemic insulin resistance. Sortilin central component the glucose transporter -Glut4 storage vesicles (GSV) which translocate to plasma membrane uptake from circulation. Here, using human adipocytes we demonstrate presence alternatively spliced, truncated sortilin variant (Sort_T) whose expression significantly increased in diabetic adipose tissue. Artificial-intelligence-based modeling,...

Objectives: To examine the role of adrenergic signaling in regulating glucose metabolism heart.Background: Glucose is a critical fuel for cardiac function. While stimulation increases contractility and its requirement increased substrate to meet energy needs, mechanisms by which receptor controls incompletely understood. Methods:Transgenic mice lacking β2AR cardiomyocytes or GRK phosphorylation serine 355/356 were developed. Ventricular myocytes isolated signaling, membrane transporter 4,...

Introduction: Sepsis is a progressive life-threatening condition in which mortality has been consistently linked to increasing organ dysfunction. We have found that activated protein C (APC) cytoprotective and anti-inflammatory properties cardiovascular disease. Whether APC critical for maintaining systemic homeostasis under sepsis aging remains unknown. Hypothesis: Administration of recombinant ameliorates sepsis-associated renal injury cardiac dysfunction via EPCR (endothelial cell...

Introduction: Metformin activates AMP-activated protein kinase (AMPK) to limit cardiac damage caused by ischemia and reperfusion (I/R). We found that a stress inducible Sesn2 is associated with AMPK maintain mitochondrial oxidative phosphorylation (OXPHOS) during I/R. But the role of Sesn2/AMPK complex in beneficial effects metformin on ischemic insults remain unknown. Hypothesis: modulates signaling cascade integrity respiration functions I/R stress. Methods: Cardiomyocyte specific knock...

Introduction: Sirtuin1 (SIRT1) serves as a deacetylase to regulate cardiac substrate metabolism during physiological and pathological conditions. The alteration in metabolic homeostasis plays critical role hypertrophic heart failure. Hypothesis: Cardiomyocyte SIRT1 modulates remodeling pressure overload-induced Methods: inducible cardiomyocyte specific Sirt1 knockout (icSirt1 -/- ) its wild type littermates (Sirt1 f/f C57BL/6J mice were subjected transverse aortic constriction (TAC) surgery...

Introduction: Cardiorenal syndrome (CRS) consists of disorders the kidneys and heart, whereby dysfunction one organ may induce other. Acute kidney injury (AKI) leads to a reduction in blood flow energy supply heart. AMP-activated protein kinase (AMPK) as an sensor regulates metabolism via interacting with scaffold Sesn2. The anti-diabetes drug metformin is AMPK agonist, it has been reported regulate substrate under physiological pathological conditions. But beneficial role CRS remains...

Introduction: The expression and secretion of cardiac MIF (macrophage migration inhibitory factor) are downregulated in aging. A small molecule agonist, MIF20 can increase the binding affinity with CD74 receptor to modulate AMPK signaling. However, pharmacological mechanisms by which triggers MIF-AMPK signaling cascade benefit heart response ischemia reperfusion (I/R) stress remain unknown. Hypothesis: rescues an impaired aging through augmenting interaction between maintain mitochondrial...

Introduction: The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. Single-Cell RNA sequencing (scRNA seq) was employed characterize transcriptional differences in various cell types between aged and young mice may contribute aged-related insult. Pyruvate Dehydrogenase Kinase 4 (Pdk4) has been shown impact capacity for fatty-acid oxidation (FAO) consequently adaption metabolic alterations of Hypothesis: Alteration Pdk4 expression levels is an...

Introduction: Obesity increases the chances of developing cardiovascular disease and strokes. The overabundance adipose tissue that occurs in obese individuals oxidative stress, which trigger upregulation antioxidant proteins, Sesn2 Nrf2. Hypothesis: Obesity-related stress triggers cardiac Nrf2 to function cardioprotective properties. Methods: Cardiomyocyte specific knock out (cSesn2 -/- ) overexpression (tTa-tet-Sesn2) C57BL/6J mice, their wildtype littermates (Sesn2 f/f tet-Sesn2) were...

Introduction: Elderly patients (age > 75) sustain larger infarcts with greater mortality from STEMI despite successful TIMI III reperfusion. age is an independent risk correction for clinical and angiographic variables. Mitochondria (MITO) are key mediators of injury during ischemia (ISC) reperfusion (R) in lab studies. The acute, transient blockade the MITO electron transport chain (ETC) at complex I R decreases infarct size adult heart models. Metformin (MET) inhibits ETC I. Hypothesis:...