A5058573517- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Alcohol Consumption and Health Effects
- Reproductive Biology and Fertility
- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Immune Response and Inflammation
- Endometriosis Research and Treatment
- Drug-Induced Hepatotoxicity and Protection
- Reproductive System and Pregnancy
- Proteoglycans and glycosaminoglycans research
- Heat shock proteins research
- Adipose Tissue and Metabolism
- Reproductive Physiology in Livestock
- Liver Disease and Transplantation
- Ultrasound and Hyperthermia Applications
- Endoplasmic Reticulum Stress and Disease
- Ovarian cancer diagnosis and treatment
- Ovarian function and disorders
- Dermatology and Skin Diseases
- Fibroblast Growth Factor Research
- Cancer Cells and Metastasis
- Pediatric Hepatobiliary Diseases and Treatments
- Adipokines, Inflammation, and Metabolic Diseases
- Diet, Metabolism, and Disease
University of Kansas Medical Center
2016-2025
University of Kansas
2013-2023
University Medical Center
2019-2021
Case Western Reserve University
2005-2013
Cleveland Clinic
2006-2013
Cleveland Clinic Lerner College of Medicine
2010
The Institute of Statistical Mathematics
2009
Roswell Park Comprehensive Cancer Center
1999-2005
Under normal physiological conditions, tissue remodeling in response to injury leads regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis - or the excess accumulation ECM can disrupt architecture function. Several organs, including heart, lung kidney, exhibit age-associated fibrosis. Here we investigated whether underlies aging ovary an organ that ages chronologically before other...
Fibrosis is a hallmark of aging tissues which often leads to altered architecture and function. The ovary the first organ show overt signs aging, including increased fibrosis in ovarian stroma. How this affects biomechanics underlying mechanisms are unknown. Using instrumental indentation, we demonstrated quantitative increase stiffness, as evidenced by an Young's modulus, when comparing ovaries from reproductively young (6-12 weeks) old (14-17 months) mice. This stiffness was dependent on...
Abstract Reactive oxygen species (ROS) contribute to the development of chronic ethanol-induced liver injury. Although ROS modulate activity many signal transduction pathways, molecular targets during ethanol exposure are not well understood. Here, we investigated whether specific ROS-sensitive pathways increased tumor necrosis factor α (TNF-α) production by Kupffer cells after feeding rats. Lipopolysaccharide (LPS) rapidly production, measured dihydrorhodamine fluorescence, in from ethanol-...
Aging is associated with reduced tissue remodeling efficiency and increased fibrosis, characterized by excess collagen accumulation altered matrix degradation.Ovulation, the process which an egg released from ovary, one of most dynamic cycles wounding repair.Because ovary first organs to age, ovulation ovarian wound healing impaired advanced reproductive age.To test this hypothesis, we induced superovulation in reproductively young old mice determined numbers eggs ovulated corpora lutea...
Chronic ethanol feeding sensitizes Kupffer cells to activation by lipopolysaccharide (LPS), leading increased production of tumor necrosis factor-alpha (TNF-alpha). Adiponectin treatment protects mice from ethanol-induced liver injury. Because adiponectin has anti-inflammatory effects on macrophages, we hypothesized that would normalize chronic sensitization LPS-mediated signals. Serum concentrations were decreased 45% in rats fed an ethanol-containing diet for 4 wk compared with pair-fed...
Background: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue skeletal muscle are two major organs utilizing in response to insulin, relative contribution these tissues impaired during chronic feeding not known. As other models resistance, such as obesity, characterized by an infiltration macrophages into tissue, well changes expression adipocytokines that play a central role regulation sensitivity, we...
Abstract The innate immune system has been implicated in the pathogenesis of alcoholic liver disease. Although immunity is usually considered an early response to injury, previous work implicating ethanol-induced injury focuses primarily on long-term ethanol exposure. We investigated period exposure determine whether there were temporal associations between activation responses and known correlates injury. Female C57BL/6 mice allowed free access ethanol-containing Lieber-DeCarli diet or...
Inflammaging is a state of chronic, low-grade inflammation associated with aging which contributes to age-related diseases. Recently, an age-associated increase in has been documented the mammalian ovary, accompanied by shift immune cell profile. In this Point View article, we consider unique population macrophage-derived multinucleated giant cells, found reproductively old mouse ovaries, as potential markers or functional drivers ovarian aging.
The ovarian stroma, the microenvironment in which female gametes grow and mature, becomes inflamed fibrotic with age. Hyaluronan is a major component of extracellular matrix (ECM), other aging tissues, accumulation low molecular weight (LMW) hyaluronan fragments can drive inflammation. Thus, we hypothesized that LMW contribute to reproductive by stimulating an inflammatory response stroma impairing gamete quality. To test this hypothesis, isolated mouse stromal cells or secondary stage...
The female reproductive system ages before any other organ in the body. This phenomenon can have tangible clinical implications leading to infertility, miscarriages, birth defects and systemic deterioration due estrogen loss. "Fibroinflammation" is a hallmark of aging tissues; there an increase inflammatory cytokines fibrotic tissue ovarian stroma. We systematically evaluated immunomodulatory factors human follicular fluid, which, like stroma, critical microenvironment directly influencing...
The effect of moderate alcohol consumption on liver fibrosis is not well understood, but evidence suggests that adenosine may play a role in mediating the effects ethanol tissue injury. Ethanol increases concentration liver. Adenosine 2A receptor (A2AR) activation known to enhance hepatic stellate cell (HSC) and A2AR deficient mice are protected from mice. Making use novel mouse model which female C57BL/6J were allowed continued access 2% (vol/vol) (11% calories) or pair-fed control diets...
Abstract Reproductive aging is associated with ovulatory defects. Age‐related ovarian fibrosis partially contributes to this phenotype as short‐term treatment anti‐fibrotic compounds improves ovulation in reproductively old mice. However, age‐dependent changes that are intrinsic the follicle may also be relevant. In study, we used a mouse model demonstrate reproductive impaired cumulus expansion which accompanied by altered morphokinetic behavior of cells assessed time‐lapse microscopy. The...
Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While component 1, Q subcomponent (C1q)-dependent activation contributes ethanol-induced injury, the alternative pathway injury unknown. Activation via classical pathways was detected hepatitis patients. Female C57BL/6J [wild type (WT)], C1q-deficient ( C1qa −/− , lacking activation), protein 4-deficient C4 lectin...
Plasminogen activator inhibitor-1 (PAI-1) is an acute phase protein that has been shown to play a role in experimental fibrosis caused by bile duct ligation (BDL) mice. However, its more severe models of hepatic (e.g., carbon tetrachloride; CCl(4)) not determined and important for extrapolation human disease. Wild-type or PAI-1 knockout mice were administered CCl(4) (1 ml/kg body wt ip) 2x/wk 4 wk. Plasma transaminase activity) histological Sirius red staining) indexes liver damage...
Reproductive aging is a robust phenotype that occurs in all females and characterized by significant reduction gamete quantity quality, which can have negative consequences on both endocrine function fertility. Age-associated differences the oocyte, follicle, ovary been well-documented, but how broader environment changes with age less well understood. Fat one of largest organs body, peri-gonadal adipose tissue surrounds rodent comprises local ovarian environment. The goal this study was to...
The extracellular matrix (ECM) is a major component of the ovarian stroma. Collagen and hyaluronan (HA) are critical stromal ECM molecules that undergo age-dependent changes in mouse human. How these components regulated organized other mammalian species with reproductive characteristics similar to women such as cows pigs, has not been systematically investigated. Therefore, we performed histological, molecular, biochemical analyses characterize collagen HA animals. Bovine ovaries had more...