scholarly journals Corticosteroid-binding globulin is a biomarker of inflammation onset and severity in female rats

2016 ◽  
Vol 230 (2) ◽  
pp. 215-225 ◽  
Author(s):  
Lesley A Hill ◽  
Tamara S Bodnar ◽  
Joanne Weinberg ◽  
Geoffrey L Hammond
Keyword(s):  
Critical Role ◽  
Clinical Signs ◽  
Experimental Period ◽  
Apparent Size ◽  
Binding Activity ◽  
Female Rats ◽  
Mrna Levels ◽  
Severe Inflammation ◽  
Corticosteroid Binding Globulin ◽  
And Function

Plasma corticosteroid-binding globulin (CBG) plays a critical role in regulating glucocorticoid bioavailability and is an acute phase ‘negative’ protein during inflammation. In an adjuvant-induced arthritis model, plasma CBG levels decrease in rats that develop severe inflammation, and we have now determined when and how these reductions in CBG occur. After administering complete Freund’s adjuvant or saline intra-dermally at the tail base, blood samples were taken periodically for 16days. In adjuvant-treated rats, decreases in plasma CBG levels matched the severity of inflammation, and decreases were observed 4days before any clinical signs of inflammation. Decreases in CBG levels coincided with an ~5kDa reduction in its apparent size, consistent with proteolytic cleavage, and cleaved CBG lacked steroid-binding activity. At the termination of the experimental period, hepatic Cbg mRNA levels were decreased in rats with severe inflammation. While plasma TNF-α increased in all adjuvant-treated rats, increases in Il-4, IL-6, IL-10, IL-13 and IFN-γ were only observed in rats with cleaved CBG. Rats with cleaved CBG also exhibited increased spleen weights, and strong negative correlations were observed among CBG, IL-6 and spleen weights, respectively. However, there were no differences in hepatic Cbg mRNA levels in relation to the apparent proteolysis of CBG, suggesting that CBG cleavage occurs before changes in hepatic Cbg expression. Our results indicate that the levels and integrity of plasma CBG are biomarkers of the onset and severity of inflammation. Dynamic changes in the levels and function of CBG likely modulate the tissue availability of corticosterone during inflammation.

scholarly journals Neuroendocrine Aging in the Female Rat: The Changing Relationship of Hypothalamic Gonadotropin-Releasing Hormone Neurons and N-Methyl-d-Aspartate Receptors**Preliminary versions of this work were presented at the 28th and 29th Annual Meetings of the Society for Neuroscience (Abstracts 110.11 and 777.10). This work was supported by the Brookdale Foundation (to A.C.G.), NIH Grant 1-PO1-AG16765–01 (to A.C.G. and J.H.M.).

Endocrinology ◽  
2000 ◽  
Vol 141 (12) ◽  
pp. 4757-4767 ◽  
Author(s):  
Andrea C. Gore ◽  
Glendy Yeung ◽  
John H. Morrison ◽  
Twethida Oung
Keyword(s):  
Critical Role ◽  
Reproductive Status ◽  
Female Rats ◽  
Mrna Levels ◽  
Female Rat ◽  
Messenger Rnas ◽  
Middle Aged ◽  
Medial Basal Hypothalamus ◽  
Aging Rats ◽  
Gnrh Neurons

Abstract The reproductive axis undergoes alterations during aging, resulting in acyclicity and the loss of reproductive function. In the hypothalamus, changes intrinsic to GnRH neurons may play a critical role in this process, as may changes in inputs to GnRH neurons from neurotransmitters such as glutamate. We investigated the effects of age and reproductive status on neuroendocrine glutamatergic NMDA receptors (NRs), their regulation of GnRH neurons, and their expression on GnRH neurons, in female rats. First, we quantified NR subunit messenger RNAs (mRNAs) in preoptic area-anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH), the sites of GnRH perikarya and neuroterminals, respectively. In POA-AH, NR1 mRNA levels varied little with age or reproductive status. NR2a and NR2b mRNA levels decreased significantly between cycling and acyclic rats. In MBH, NR mRNAs all increased with aging, particularly in acyclic animals. Second, we tested the effects of N-methyl-d,l-aspartate (NMA) on GnRH mRNA levels in POA-AH of aging rats. NMA elevated GnRH mRNA levels in young rats, but decreased them in middle-aged rats. Third, we quantified expression of the NR1 subunit on GnRH perikarya in aging rats using double label immunocytochemistry. NR1 expression on GnRH cell bodies varied with age and reproductive status, with 30%, 19%, and 46% of GnRH somata double labeled with NR1 in young proestrous, middle-aged proestrous, and middle-aged persistent estrous rats, respectively. Thus, 1) the expression of hypothalamic NR subunit mRNAs correlates with reproductive status; 2) changes in NR subunit mRNA levels, if reflected by changes in protein levels, may result in alterations in the stoichiometry of the NR during aging, with possible physiological consequences; 3) the effects of NR activation on GnRH mRNA switches from stimulatory to inhibitory during reproductive aging; and 4) expression of the NR1 subunit on GnRH perikarya changes with reproductive status. These molecular, physiological, and cellular neuroendocrine changes are proposed to be involved in the transition to acyclicity in aging female rats.

scholarly journals O-Polysaccharide Glycosylation Is Required for Stability and Function of the Collagen Adhesin EmaA of Aggregatibacter actinomycetemcomitans

2012 ◽  
Vol 80 (8) ◽  
pp. 2868-2877 ◽  
Author(s):  
Gaoyan Tang ◽  
Teresa Ruiz ◽  
Keith P. Mintz
Keyword(s):  
Cellular Localization ◽  
Proteolytic Enzymes ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Binding Activity ◽  
Mrna Levels ◽  
Collagen Binding ◽  
Content Type ◽  
Protein Levels ◽  
Mutant Strains ◽  
And Function

ABSTRACTAggregatibacter actinomycetemcomitansis hypothesized to colonize through the interaction with collagen and establish a reservoir for further dissemination. The trimeric adhesin EmaA ofA. actinomycetemcomitansbinds to collagen and is modified with sugars mediated by an O-antigen polysaccharide ligase (WaaL) that is associated with lipopolysaccharide (LPS) biosynthesis (G. Tang and K. Mintz, J. Bacteriol.192:1395–1404, 2010). This investigation characterized the function and cellular localization of EmaA glycosylation. The interruption of LPS biogenesis by using genetic and pharmacological methods changed the amount and biophysical properties of EmaA molecules in the outer membrane. InrmlCandwaaLmutant strains, the membrane-associated EmaA was reduced by 50% compared with the wild-type strain, without changes in mRNA levels. The membrane-associated EmaA protein levels were recovered by complementation with the corresponding O-polysaccharide (O-PS) biosynthetic genes. In contrast, another trimeric autotransporter, epithelial adhesin ApiA, was not affected in the same mutant background. The inhibition of undecaprenyl pyrophosphate recycling by bacitracin resulted in a similar decrease in the membrane-associated EmaA protein. This effect was reversed by removal of the compound. A significant decrease in collagen binding activity was observed in strains expressing the nonglycosylated form of EmaA. Furthermore, the electrophoretic mobility shifts of the EmaA monomers found in the O-PS mutant strains were associated only with the membrane-associated protein and not with the cytoplasmic pre-EmaA protein, suggesting that this modification does not occur in the cytoplasm. The glycan modification of EmaA appears to be required for collagen binding activity and protection of the protein against degradation by proteolytic enzymes.

Increased SUMOylation of TCF21 improves its stability and function in human endometriotic stromal cells

2021 ◽  
Author(s):  
Jingwen Zhu ◽  
Peili Wu ◽  
Cheng Zeng ◽  
Qing Xue
Keyword(s):  
Stromal Cells ◽  
Critical Role ◽  
Protein A ◽  
Binding Activity ◽  
Vital Role ◽  
Upstream Stimulatory Factor ◽  
Ovarian Endometriosis ◽  
Steroidogenic Factor 1 ◽  
Ginkgolic Acid ◽  
And Function

Abstract Endometriosis is an estrogen-dependent disease. Our previous study demonstrated that elevated levels of transcription factor 21 (TCF21) in endometriotic tissues enhanced steroidogenic factor-1 (SF-1) and estrogen receptor β (ERβ) expression by forming a heterodimer with upstream stimulatory factor 2 (USF2), allowing these TCF21/USF2 complexes to bind to the promoters of SF-1 and ERβ. Furthermore, TCF21 contributed to the increased proliferation of endometriotic stromal cells (ESCs), suggesting that TCF21 may play a vital role in the pathogenesis of endometriosis. SUMOylation is a posttranslational modification that has emerged as a crucial molecular regulatory mechanism. However, the mechanism regulating TCF21 SUMOylation in endometriosis is incompletely characterized. Thus, this study aimed to explore the effect of TCF21 SUMOylation on its expression and regulation in ovarian endometriosis. We found that the levels of SUMOylated TCF21 were increased in endometriotic tissues and stromal cells compared with eutopic endometrial tissues and stromal cells and enhanced by estrogen. Treatment with the SUMOylation inhibitor ginkgolic acid (GA) and the results of a protein half-life assay demonstrated that SUMOylation can stabilize the TCF21 protein. A coimmunoprecipitation (Co-IP) assay showed that SUMOylation probably increased its interaction with USF2. Further analyses elucidated that SUMOylation of TCF21 significantly increased the binding activity of USF2 to the SF-1 and ERβ promoters. Moreover, the SUMOylation motifs in TCF21 affected the proliferation ability of ESCs. The results of this study suggest that SUMOylation plays a critical role in mediating the high expression of TCF21 in ESCs and may participate in the development of endometriosis.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

The effect of dexamethasone on mucosal immunity of uterine tissue during pregnancy in rat

2019 ◽  
Vol 20 (1) ◽  
pp. 75-84
Keyword(s):  
Early Pregnancy ◽  
Histopathological Examination ◽  
Early Period ◽  
Interleukin 10 ◽  
Treated Group ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Uterine Tissue ◽  
Leukocytic Infiltration

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy

scholarly journals The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

2021 ◽  
Author(s):  
Valentin Sencio ◽  
Marina Gomes Machado ◽  
François Trottein
Keyword(s):  
Gut Microbiota ◽  
Bacterial Infections ◽  
Respiratory Infections ◽  
Critical Role ◽  
Good Health ◽  
Disease Outcomes ◽  
And Function ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Viral Respiratory

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

scholarly journals Identification of Risk Factors for Lameness Detection with Help of Biosensors

Agriculture ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 610
Author(s):  
Ramūnas Antanaitis ◽  
Vida Juozaitienė ◽  
Gediminas Urbonavičius ◽  
Dovilė Malašauskienė ◽  
Mindaugas Televičius ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Milk Fat ◽  
Milk Protein ◽  
Standard Procedure ◽  
Clinical Signs ◽  
Experimental Period ◽  
Early Lactation ◽  
Protein Ratio ◽  
Walking Activity ◽  
Protein Milk

In this study we hypothesized that the lameness of early lactation dairy cows would have an impact on inline biomarkers, such as rumination time (RT), milk fat (%), milk protein (%), milk fat/protein ratio (F/P), milk lactose (L, %), milk electrical conductivity of all udder quarters, body weight (BW), temperature of reticulorumen content (TRR), pH of reticulorumen content (pH), and walking activity (activity). All 30 lame cows (LCs) used in this experiment had a score of 3–4, identified according to the standard procedure of Sprecher et al.. The 30 healthy cows (HC) showed a lameness score of one. RT, milk fat, MY, milk protein, F/P, L, milk electrical conductivity of all udder quarters, and BW were registered using Lely Astronaut® A3 milking robots each time the cow was being milked. The TRR, cow activity, and pH of the contents of each cow’s reticulorumen were registered using specific smaXtec boluses. The study lasted a total of 28 days. Days “−14” to “−1” denote the days of the experimental period before the onset of clinical signs of lameness (day “0”), and days “1” to “13” indicate the period after the start of treatment. We found that from the ninth day before the diagnosis of laminitis until the end of our study, LCs had higher milk electrical conductivity in all udder quarters, and higher milk fat to protein ratios. On the 3rd day before the onset of clinical signs of the disease until the day of diagnosis, the milk fat of the LC group was reduced. The activity of the LCs decreased sharply from the second day to the first day after treatment. RT in the HC group tended to decrease during the experiment. pH in LCs also increased on the day of the appearance of clinical signs.

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

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