It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. In order to examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (Tb) in a mouse model of porphyria ...

Lenalidomide is a potent immunomodulatory agent capable of downregulating proinflammatory cytokines such as TNF-α and up-regulating anti-inflammatory cytokines. Lenalidomide has been shown to elicit cardiovascular effects although its impact on cardiac function remains obscure. This study was designed to examine the effect of lenalidomide on cardiac contractile function in ob/ob ...

CYP2A13, CYP2B6, and CYP2F1, neighboring cytochrome P450 (P450) genes on human chromosome 19, are active in the metabolic activation of many drugs, respiratory toxicants, and chemical carcinogens. In efforts to facilitate studies on the regulation and function of these human genes, we have generated a CYP2A13/2B6/2F1-transgenic (TG) mouse (all *1 ...

We have previously established a cytochrome P450 4F2 (CYP4F2) transgenic mouse model. The present study elucidated the molecular foundation of hypertension by androgen-induction in this model. The renal expression of CYP4F2 in transgenic mice was highly expressed and strongly induced with 5α-dihydrotestosterone (DHT) treatment determined by Western blot. DHT also ...

We have previously characterized lipocalin 2 (Lcn2) as a new adipokine having a critical role in energy and lipid metabolism in male mice. Previous studies by others have suggested that Lcn2 is a putative target gene of estrogens. In this study, we reported the effect of Lcn2 deficiency on estradiol ...

In both rats and mice, an acute skeletal muscle injury leads to leukocyte infiltration in which the leukocytes remove dead fibers and cellular debris, induce a secondary injury, and/or promote myofiber regeneration. Short-term exogenous estrogen treatment attenuates this leukocyte infiltration and prevents body weight gain in rat exercise-induced skeletal muscle ...

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of ...

The dichotomous anxiogenic and anxiolytic properties of estrogens have been reported to be mediated by two distinct neural estrogen receptors (ER), ERα and ERβ, respectively. Using a combination of pharmacological and genetic approaches, we confirmed that the anxiolytic actions of estradiol are mediated by ERβ and extended and these observations ...

Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used (C57BL/6xSJL)F1 mice transgenic for ...

Sex differences exist in the hypertrophic response, cardiac remodeling, and transition to heart failure of hypertensive patients, and while some of these differences are likely influenced by estrogen, the genetic pathways downstream of estrogen that impact on cardioprotection have yet to be fully elucidated. We have previously shown that the ...

PURPOSE: Obesity increases the risk of diabetes. The dysregulation of estrogen metabolism has been associated with the susceptibility to obesity and diabetes. Here, we explore the role estrogen plays in sex differences in obesity and glucose metabolism, specifically adipocyte biology. METHODS: We randomized C57BL/6 J male, non-ovariectomized female, ovariectomized female, and ...

The dioxin/aryl hydrocarbon receptor (AhR) mediates most toxic effects of dioxins. In utero/lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fetal/neonatal development and the developing male reproductive tract are among the most sensitive tissues. TCDD causes antiestrogenic responses in rodent mammary gland and uterus and in human breast cancer cell lines in ...

ABSTRACT: BACKGROUND: The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha-zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from ...

OBJECTIVE: Mechanisms underlying gender difference of atherogenesis were investigated focusing on direct effects of estrogen on the artery. METHODS: First, male and female apoE(-/-) mice were fed an atherogenic diet for 16 weeks from 10 weeks of age. Second, female apoE(-/-) mice were ovariectomized (ovx) or sham operated at 8 ...

Wound healing (WH) impairment is a well-documented phenomenon in clinical and experimental diabetes. Sex hormones, in addition to a number of signaling pathways including transforming growth factor-β1 (TGF-β1)/Smads and TNF-α/NF-κB in macrophages and fibroblasts, appear to play a cardinal role in determining the rate and nature of WH. We hypothesized ...

Aims: Obesity is associated with insulin resistance, liver steatosis, and low-grade inflammation. The role of estrogen in sex differences in the above comorbidities is not fully understood. Our aim was to assess the role estrogen has in modulating adipocyte size, adipose tissue oxidative stress, inflammation, insulin resistance, and liver steatosis. ...

Gender differences in both vulnerability to stroke and outcome following cerebral ischaemia have frequently been observed and attributed to the action of steroid hormones. Progesterone is a candidate neuroprotective factor for stroke; however, studies are lacking which: (i) study those groups representing high risk i.e. postmenopausal females; (ii) administer progesterone ...

Gender-related differences in medulloblastoma (MB) development have been reported with a higher incidence in males (slightly above 60%) than in females, female gender being also a significantly favorable prognostic factor in MB. The present study focused on the evaluation of the mechanisms by which estrogens protect against MB formation. To ...

Knockout of the Cyp-19 gene (aromatase) renders mice to have insufficient endogenous estrogen production and contributes to the development of symptoms related the metabolic syndrome, including excess adiposity and insulin resistance. This study comparatively assessed the estrogen responsiveness in animal models of genetical versus surgical (ovariectomy) origin of estrogen deficiency. ...

BACKGROUND: Ileocolonic luminal pH has been reported to be abnormally low in inflammatory bowel disease (IBD) patients, and one of the causative factors may be reduced epithelial HCO 3- secretory rate (J HCO3 -). Disturbances in J HCO3 - may occur due to inflammation-induced changes in the crypt and villous architecture, or due to the ...

ABSTRACT: BACKGROUND: Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD) in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG) and azathioprine (AZA) in a murine model of ...

Phosphoinositide 3-kinase-γ (PI3Kγ) is implicated in many pathophysiological conditions, and recent evidence has suggested its involvement in colitis. In the present study, we investigated the effects of AS605240, a relatively selective PI3Kγ inhibitor, in experimental colitis and its underlying mechanisms. Acute colitis was induced in mice by treatment with trinitrobenzene ...

BACKGROUND: Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced the activity of regulatory T cells (Tregs) in vitro. The aim of the present work was to demonstrate if L. acidophilus NCFM™ also affects the function of Tregs in vivo. METHODS: Development of ...

BACKGROUND: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn's disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. METHODS: C57BL/6 mice were injected (i.v.) with ...

Genetic modifier loci influence the phenotypic expression of many Mendelian traits; insight into disease pathogenesis gained from their identification in animal disease models may impact the treatment of human multigenic disorders. We previously described an innate immune-driven model of spontaneous ulcerative colitis in T-bet(-/-).Rag2(-/-) double-deficient mice that resembles human ulcerative ...

BACKGROUND: Helminth infection has been proven to reduce the severity of experimental inflammatory bowel disease (IBD). The excretory-secretory proteins of helminths play an important role in the process of immunomodulation. AIMS: In the present study, we aimed to investigate the protective potential of recombinant Trichinella spiralis (TS) 53-kDa protein (rTsP53), ...

Macrophages promote tissue injury or repair depending upon on their activation status and the local cytokine milieu. It remains unclear whether the immunosuppressive effects of transforming growth factor beta (TGF-β) serve a non-redundant role in macrophage function in vivo. We generated macrophage-specific transgenic mice that express a truncated TGF-β receptor ...

Fibrogenic mesenchymal cells including fibroblasts and myofibroblasts play a key role in intestinal fibrosis, however, their precise role is largely unknown. To investigate their role in intestinal fibrosis, we analyzed the lesions of chronic colitis in C57BL/6 (B6) mice induced by dextran sulfate sodium (DSS). B6 mice exposed to single ...

Expression of the transmembrane glycoprotein CD98 (encoded by SLC3A2) is increased in intestinal inflammatory conditions, such as inflammatory bowel disease (IBD), and in various carcinomas, yet its pathogenetic role remains unknown. By generating gain- and loss-of-function mouse models with genetically manipulated CD98 expression specifically in intestinal epithelial cells (IECs), we ...

OBJECTIVE: The purpose of this study was to investigate the role of the PI3K/Akt signaling pathway in the pathogenesis of ulcerative colitis (UC). MATERIALS AND METHODS: Mucosal biopsy specimens from 54 active UC cases and adjacent normal tissues from 18 colon cancer cases were investigated. Twenty-eight Balb/c mice were randomly ...

Although fluoxetine, a selective serotonin reuptake inhibitor, is known to demonstrate anti-inflammatory activity, little information is available on the effect of fluoxetine regarding intestinal inflammation. This study investigates the role of fluoxetine in the attenuation of acute murine colitis by suppression of the NF-κB pathway in intestinal epithelial cells (IEC). ...

Dipeptidyl-peptidase IV (DPP-IV) inhibitors are expected to prolong the half-life of Glucagon-like peptide (GLP-2) as well as GLP-1, and may result in the promotion of epithelial cell proliferation and regeneration. The aim of this study was to investigate whether a DPP-IV inhibitor can promote epithelial proliferation and attenuate dextran sodium ...

NHE3, the major intestinal Na(+)/H(+) exchanger was shown to be downregulated and/or inhibited in IBD patients, a phenomenon believed to contribute to inflammation-associated diarrhea. NHE3(-/-) mice spontaneously develop colitis and demonstrate high susceptibility to dextran sulfate-induced mucosal injury. In this study, we investigated the effects of NHE3 deficiency on the ...

Abstract Objective. Intrarectal treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS), an inducer of intestinal inflammation, in mice increases the population size of Enterobacteriaceae, particularly Klebsiella pneumoniae, while reducing the population size of lactic acid bacteria. Therefore, we investigated the effects of these bacteria in TNBS-induced colitis in mice. Material and methods. ...

Fine-tuning of host cell responses to commensal bacteria plays a crucial role in maintaining homeostasis of the gut. Here, we show that tumor necrosis factor receptor-associated factor (Traf)2(-/-) mice spontaneously developed severe colitis and succumbed within 3 weeks after birth. Histological analysis revealed that apoptosis of colonic epithelial cells was ...

BACKGROUND: Mesenchymal stem cells, which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSC) could ameliorate colitis in a ...

Ethnopharmacological relevance: In traditional Korean medicine, Bojanggunbi-tang (BGT), which consists of 16 herbs, is one of the most frequently used herbal prescriptions in South Korea for treating intestinal disorders such as colitis. AIM OF THE STUDY: : This study investigated whether BGT could show a protective action on 2 different ...

The effects of the soy isoflavones, genistein, daidzein and equol, on experimental colitis were examined. Equol severely perpetrated dextran sulfate sodium (DSS)-induced colitis as evaluated by the weight loss. Production of the anti-inflammatory cytokine, IL-10, from T cells was decreased in the equol-treated mice. The results show that the soy ...

Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that ...

Clostridium difficile is the major cause of antibiotic-associated colitis, a disease with significant morbidity and mortality. This study investigated the role of the hemeoxygenase-1 (HO-1)/carbon monoxide (CO) pathway in C. difficile toxin A-induced enteritis in mice. Hemin, HO substrate, zinc protoporphyrin IX (ZnPP IX), a specific HO-1 inhibitor, dimanganese decacarbonyl ...

The dextran sulfate sodium (DSS) model of colitis has been commonly utilized in mice to assess novel treatments for ulcerative colitis. Recent studies have indicated that morphological and biochemical changes extend to the small intestine (SI). This study aimed to characterize histological and biochemical changes in the SI during DSS ...

The aim of the present study was to examine the effects of natural almond skin (NS) powder in mice subjected to experimental colitis. Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). NS powder was administered daily orally (30mg/kg). Four days after DNBS administration, colon NF-κB ...

Inflammatory bowel disease (IBD) is related to dysfunction of intestinal immunity. Neutrophils have an important role in innate immunity via the oxidative burst, using the p47phox- and gp91(phox)-containing NAD(P)H oxidase known as Nox2. In dextran sulphate sodium (DSS)-induced colitis, no significant difference in inflammation between p47(phox-/-) and wild-type (WT) mice ...

Syndecan-1, the most abundant heparan sulfate proteoglycan in the gastrointestinal tract, is reduced in the regenerative epithelium in inflammatory bowel disease (IBD). This study explored the effects of the immunomodulator glatiramer acetate (GA, Copaxon) treatment on syndecan-1 expression in dextran sodium sulphate (DSS) induced colitis. Acute and chronic colitis was ...

Milk fat globule-EGF factor 8 (MFG-E8) has been shown to play an important role in maintaining the integrity of the intestinal mucosa and accelerate healing of the mucosa in septic mice. Herein, we (1) analyzed the expression of MFG-E8 in the gut of wild type C57BL/6 (MFG-E8(+/+)) mice with and ...

Background and Aim:  Probiotics are used in the therapy of inflammatory bowel disease. This study aimed to determine the effects of probiotic Lactobacillus plantarum LP-Onlly (LP) on gut flora and colitis in interleukin-10 knockout (IL-10(-/-) ) mice, a model of spontaneous colitis. Methods:  IL-10(-/-) and wild-type mice were used at ...

Dextran sulfate sodium (DSS) is commonly used in rodent IBD models to chemically induce acute intestinal inflammation. The acute course of colitis includes colon tissue damages and recovery from wounded tissues. As skin wound repair was delayed by splenectomy, we asked whether splenectomy would induce the delay of colonic wound ...

To assess the anti-inflammatory effect of the probiotic Bifidobacterium lactis (B. lactis) in an adoptive transfer model of colitis. Donor and recipient mice received either B. lactis or bacterial culture medium as control (deMan Rogosa Sharpe) in drinking water for one week prior to transfer of a mix of naive ...

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) which etiology has not yet been fully clarified. Cytokine interleukin-10 (IL-10) plays a central role in down-regulating inflammatory cascade in UC and is likely a candidate for therapeutic intervention. However, its intravenous administration is costly and inconvenient. Therefore, we established a ...

BACKGROUND: Depression is common in patients with inflammatory bowel disease (IBD) but the pathway is not well understood. We examined whether the locus of susceptibility to colitis in mice with depression-like behavior (DLB) resides with the macrophage and implicates the vagus nerve. METHODS: Chronic colitis mimicking ulcerative colitis (UC) was ...