A5072669719- Sepsis Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatitis Pathology and Treatment
- Immune Response and Inflammation
- Intensive Care Unit Cognitive Disorders
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Vitamin C and Antioxidants Research
- Pancreatic and Hepatic Oncology Research
- Neuropeptides and Animal Physiology
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Regulation of Appetite and Obesity
- Biomarkers in Disease Mechanisms
- Neuroendocrine Tumor Research Advances
- Acute Kidney Injury Research
- Respiratory Support and Mechanisms
- Pharmacological Effects of Natural Compounds
- Intracerebral and Subarachnoid Hemorrhage Research
- Glutathione Transferases and Polymorphisms
- Vibrio bacteria research studies
- Nutrition and Health in Aging
- Diabetic Foot Ulcer Assessment and Management
University of Kentucky
2015-2024
Boston University
2016
Markey Cancer Center
2010-2013
The University of Texas Medical Branch at Galveston
2008-2012
Sepsis, a life-threatening systemic inflammatory response syndrome induced by infection, is widely studied using laboratory animal models. While cecal-ligation and puncture (CLP) considered the gold standard model for sepsis research, it may not be preferable experiments comparing animals of different size or under dietary regimens. By cecum size, shape, cecal content characteristics in mice experimental conditions (aging, diabetes, pancreatitis), we show that variability could problematic...
Increased mortality and overexpression of interleukin-6 (IL-6) during inflammatory stress are well-documented age-associated phenomena; however, the site IL-6 is not entirely known. Here, we report that white adipose tissue a major source in aged animals lipopolysaccharide (LPS)-induced systemic inflammation. Among various tissues examined, from epididymal fat pad (located abdominal cavity) expressed highest level messenger RNA both young mice with 5.5-fold higher aged. Immunohistochemistry...
S-nitrosylation of the deacetylase SIRT1 functions as a proinflammatory switch in aging and inflammatory disorders.
Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development new functional limitations that persist for years. To delineate mechanisms sepsis-induced weakness, we first surpassed barrier by establishing murine model with ICU-like interventions allows the study survivors. We show have profound at least 1 month, even after recovery mass. Abnormal mitochondrial ultrastructure, impaired...
Expression of interleukin-6 (IL-6) upon acute inflammatory stress is significantly augmented by aging in adipose tissue, a major source this cytokine. In the present study, we examined mechanism age-dependent IL-6 overproduction using visceral white tissue from C57BL/6 mice. Upon treatment with lipopolysaccharide (LPS) vitro, was produced explants, and secreted levels were higher cultures aged (24 months) mice compared to young (4 months). Interleukin 1 beta (IL-1β) tumor necrosis factor...
Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ-induces expression the transcription Forkhead box S1 (FOXS1) in hepatocytes may have a role pathogenesis hepatocellular carcinoma (HCC). To date, no studies determined how it affects HSCs. We analyzed human livers cirrhosis, HCC, murine model found that FOXS1 is significantly higher fibrotic but not HCC....
Abstract Adipose tissue dysfunction is strongly linked to the development of chronic inflammation and cardiometabolic disorders in aging. While much attention has been given role resident adipose immune cells disruption homeostasis obesity, age-specific effects remain understudied. Here, we identified characterized a population γδ T cells, which show unique age-dependent accumulation visceral (VAT) both mice humans. Diet-induced obesity likewise increased cell numbers; however, effect was...
Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and positively correlate disease severity mortality. Our prior work demonstrated that PAI-1 is associated acute kidney injury (AKI) septic mice. The objective this study was to determine if causally related AKI worse outcomes using a clinically-relevant age-appropriate murine model sepsis. Sepsis induced by cecal slurry (CS)-injection wild-type (WT, C57BL/6) knockout (KO) mice at...
Objectives: Visceral adipose tissue is a major site for expression of proinflammatory and procoagulant genes during acute systemic inflammation. In this study, we tested whether the loss fat mass by dietary restriction would remove source these factors resulting in improved tolerance to sepsis endotoxemia. Design: Prospective, laboratory controlled experiments. Setting: Aging critical care research university hospital. Subjects: Middle-aged (12-month old) male C57BL/6 mice. Interventions:...
Tolerance to physiological stress resulting from inflammatory disease decreases significantly with age. High mortality rates, increased cytokine production, and pronounced thrombosis are characteristic complications of aged mice acute systemic inflammation induced by injection lipopolysaccharide (LPS). As adipose tissue is now recognized as an important source cytokines, we determined the effects aging on visceral white gene expression during LPS-induced in male C57BL/6 mice. Microarray...
Current animal models of sepsis often incorporate antibiotics to be consistent with clinical standards for treatment patients in the intensive care unit. However, such experimental intervention is commonly initiated very early after infectious insult, which likely blunts progression systemic inflammation and downstream pathology. The objective this study was establish an model delayed therapeutic intervention, allowing a longer disease course pathology, but still resulting high survival...
The severity and mortality rates of acute pancreatitis (AP) are significantly elevated in the elderly population. However, due to a lack appropriate animal models, underlying mechanisms for this age-dependent vulnerability remain largely unknown. purpose study was characterize murine model AP, which displays age-associated severity, use identify pathophysiologies that distinctive aged with AP. AP induced young (4-5 months), middle-aged (12-13 (23-25 months) C57BL/6 mice by repeated injection...
It is widely accepted that food consumption in humans declines with advanced age; however, data from mice remain controversial. Based on our previous observation spill a considerable amount of while eating, we hypothesized increased spillage old masks actual intake. To investigate whether exhibit age-associated consumption, evaluated the C57BL/6 at various ages by measuring both receptacle and dropped to cage bottom during feeding. We found significantly more (36% ± 8%) than young (18% 5%),...
γδ T cells are resident in visceral adipose tissue (VAT) where they show an age-associated increase numbers and contribute to local systemic chronic inflammation. However, regulation of this population mechanisms for the age-dependent accumulation not known. In study, we identified a progressive trend cell VAT over lifespan mice explored physiological contributing accumulation. Using isochronic parabiotic pairs wild-type (WT) receptor delta knockout (TCRδ KO) at young old age, confirmed that...
Serum amyloid A (SAA) is a family of proteins, the plasma levels which may increase >1000-fold in acute inflammatory states. We investigated role SAA sepsis using mice deficient all three acute-phase isoforms (SAA-TKO). deficiency significantly increased mortality rates experimental mouse models: cecal ligation and puncture (CLP), slurry (CS) injection, lipopolysaccharide (LPS) treatments. SAA-TKO had exacerbated lung pathology compared to wild-type (WT) after CLP. bulk RNA sequencing...
Sepsis is a life-threatening clinical condition that particularly serious among the elderly who experience considerably higher mortality rates compared with younger patients. Using sterile endotoxemia model, we previously reported age-dependent in conjunction enhanced coagulation and insufficient levels of anti-coagulant factor activated protein C (aPC). The purpose present study was to further investigate mechanisms for aPC insufficiency during experimental sepsis. Intra-abdominal sepsis...
Neurotensin (NT), an intestinal peptide secreted from N cells in the small bowel, regulates a variety of physiological functions gastrointestinal tract, including secretion, gut motility, and growth. The class IA phosphatidylinositol 3-kinase (PI3K) family, which comprised p110 catalytic (α, β δ) p85 regulatory subunits, has been implicated regulation hormone secretion endocrine cells. However, underlying mechanisms remain poorly understood. In particular, role PI3K is not known. Here, we...
Natural killer (NK) lymphocyte-mediated cytotoxicity and cytokine secretion control infections cancers, but these crucial activities decline with age. NK cell development, homeostasis, function require IL-15 its chaperone, Receptor alpha (IL-15Rα). Macrophages (Mφ) dendritic cells (DC) are major sources of proteins. We had previously postulated that additional IL-15Rα is made by skeletal muscle adipose tissue. These may be important in aging, when IL-15-producing immune decline. circulate...
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is important for tissue proliferation. Previously, we found that regeneration after partial pancreatic resection was markedly attenuated in aged mice as compared to young and this attenuation because of an age-dependent reduction PI3K/Akt signaling the acini; however, mechanisms age-associated decline remained unknown. To better delineate decreased activation with aging, changes cell proliferation were investigated present study using...