Evaluation of Some Potential New Serological and Faecal Markers in Canine Lymphangiectasia: Correlation with Mucosal Morphology and Histological Score

2020 ◽  
Vol 174 ◽  
pp. 173
Author(s):  
G. Rossi ◽  
M. Cerquetella ◽  
S. Berardi ◽  
L. Galosi ◽  
S. Mari ◽  
...  
Keyword(s):  
Histological Score ◽  
Mucosal Morphology

scholarly journals Exposures to 2,4-Dichlorophenoxyacetic acid with or without endotoxin upregulate small cell lung cancer pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Geetika Kaur ◽  
B. V. Sunil Kumar ◽  
Baljit Singh ◽  
R. S. Sethi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Lung Inflammation ◽  
Low Dose ◽  
Small Cell ◽  
Dichlorophenoxyacetic Acid ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Histological Score ◽  
2,4 Dichlorophenoxyacetic Acid

Abstract Background Pesticide residues in food and environment along with airborne contaminants such as endotoxins pose health risk. Although herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) has been associated with increased risk of lung cancers such as small cell lung cancer (SCLC) among agricultural workers, there are no data on the SCLC signaling pathway upon 2,4-D exposure without LPS or in combination with endotoxin. Methods We exposed Swiss albino mice (N = 48) orally to high (9.58 mg kg− 1) and low (5.12 mg kg− 1) dosages of 2,4-D dissolved in corn oil for 90 days followed by E. coli lipopolysaccharide (LPS) or normal saline solution (80 μl/animal). Lung samples and broncho-alveolar fluid (BALF) were subjected to Total histological score (THS) and total leucocyte count (TLC) and differential leucocytes count (DLC) analyses, respectively. We used microarray and bioinformatics tools for transcriptomic analyses and differentially expressed genes were analyzed to predict the top canonical pathways followed by validation of selected genes by qRT-PCR and immunohistochemistry. Results Total histological score (THS) along with BALF analyses showed lung inflammation following long term dietary exposure to high or low doses of 2,4-D individually or in combination with LPS. Microarray analysis revealed exposure to high dose of 2,4-D without or with LPS upregulated 2178 and 2142 and downregulated 1965 and 1719 genes, respectively (p < 0.05; minimum cut off 1.5 log fold change). The low dose without or with LPS upregulated 2133 and 2054 and downregulated 1838 and 1625 genes, respectively. Bioinformatics analysis showed SCLC as topmost dysregulated pathway along with differential expression of Itgb1, NF-κB1, p53, Cdk6 and Apaf1. Immunohistological and quantitative real time PCR (qRT-PCR) analyses also supported the transcriptomic data. Conclusions Taken together, the data show exposures to high and low dose of 2,4-D with/without LPS induced lung inflammation and altered pulmonary transcriptome profile with the involvement of the SCLC pathway. The data from the study provide the insights of the potential damage on lungs caused by 2,4-D and help to better understand the mechanism of this complex relation.

scholarly journals A32 EMPAGLIFOZIN IMPROVES GASTROINTESTINAL INFLAMMATION IN A MOUSE MODEL OF COLITIS

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 213-215
Author(s):  
K Madsen ◽  
H Dang ◽  
N Hotte ◽  
V Mocanu ◽  
M Ferdaoussi ◽  
...  
Keyword(s):  
Animal Model ◽  
Sglt2 Inhibitor ◽  
Direct Effects ◽  
Lipocalin 2 ◽  
Wild Type ◽  
Gut Inflammation ◽  
Beneficial Effects ◽  
Histological Score ◽  
Cytokine Levels ◽  
Gastrointestinal Inflammation

Abstract Background Empagliflozin (EMPA) is a highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor and is increasingly being utilized as an antihyperglycemic agent in the management of type 2 diabetes. Interestingly, it has been demonstrated in human trials that EMPA treatment exerts potent cardioprotective effects by reducing cardiac inflammation independently of glycemic control. Further, EMPA has also been shown to suppress LPS-induced renal and systemic inflammation in an animal model. Based on these findings, we hypothesized that EMPA treatment may also be effective in reducing gut inflammation. Aims The aim of this study was to examine the effects of treatment with EMPA on gastrointestinal inflammation in an animal model of inflammatory bowel disease and to determine mechanistic insights regarding its direct effects on gut cytokine secretion. Methods Adult male and female IL-10-/- mice with established colitis were treated with a daily gavage of EMPA (10mg/kg; n=10) or vehicle (n=10) for 14 days. Disease activity was assessed by measurement of mouse weight, colonic weight and length, histological score, cytokine levels in colonic homogenate and lipocalin-2 levels in stool. To examine for possible direct effects of EMPA, colonic explants from wild-type (n=8) and IL-10-/- (n=8) mice were incubated with increasing doses of EMPA (0.1–5 µM) ± LPS (10µg/ml) for 2 hours and tissue levels of IL-1β and TNFα protein measured by ELISA. Results After 14 days EMPA treated IL-10-/- mice had a significant improvement in colonic inflammation as evidenced by decreased colonic weight to length ratio (p=0.019), decreased fecal lipocalin-2 (p=0.03), as well as decreased enterocyte injury (p=0.01), decreased lamina propria neutrophils (p=0.01) and decreased total histological score (p=0.006). EMPA treated mice also maintained their weight over the 14 days while untreated mice continued to lose weight (p=0.04). There were no significant differences in colonic homogenate levels of TNFα, IL-1β, or IL-6 or in blood glucose levels between EMPA-treated mice and controls. In addition, EMPA did not suppress levels of basal or LPS-induced TNFα and IL-1β in colonic explants from either wild-type or IL-10-/- mice suggesting that the beneficial effects in IL-10-/- mice were not due to direct effects of EMPA on colonic TNFα or IL-1β cytokine levels. Conclusions EMPA treatment dramatically improved histologic and fecal inflammatory markers and maintained body weight in adult IL-10-/- mice with established colitis. These findings suggest further investigations into the effects of EMPA in treating gut inflammation are warranted. Funding Agencies CAG, CIHR

Goblet Cell Hyperplasia is not Epithelial-Autonomous in the Cftr Knockout Intestine

2021 ◽  
Author(s):  
Nancy M Walker ◽  
Jinghua Liu ◽  
Sarah M Young ◽  
Rowena A Woode ◽  
Lane L. Clarke
Keyword(s):  
Cell Differentiation ◽  
Goblet Cell ◽  
Ex Vivo ◽  
Cell Hyperplasia ◽  
Goblet Cell Hyperplasia ◽  
Cell Numbers ◽  
Markers Of Inflammation ◽  
Tlr4 Agonist ◽  
Goblet Cell Differentiation ◽  
Mucosal Morphology

Goblet cell hyperplasia is an important manifestation of cystic fibrosis (CF) disease in epithelial-lined organs. Explants of CF airway epithelium show normalization of goblet cell numbers; therefore we hypothesized that small intestinal enteroids from Cftr knockout (KO) mice would not exhibit goblet cell hyperplasia. Toll-like receptors 2 and 4 (Tlr2, Tlr4) were investigated as markers of inflammation and influence on goblet cell differentiation. Ex vivo studies found goblet cell hyperplasia in Cftr KO jejunum as compared to wild-type (WT). IL-13, SAM pointed domain-containing ETS transcription factor (Spdef), Tlr2 and Tlr4 protein expression was increased in Cftr KO intestine relative to WT. In contrast, WT and Cftr KO enteroids did not exhibit differences in basal or IL-13-stimulated goblet cell numbers, or differences in expression of Tlr2, Tlr4 and Spdef. Ileal goblet cell numbers in Cftr KO/Tlr4 KO and Cftr KO/Tlr2 KO mice were not different from Cftr KO mice, but enumeration was confounded by altered mucosal morphology. Treatment with Tlr4 agonist LPS did not affect goblet cell numbers in WT or Cftr KO enteroids, whereas the Tlr2 agonist Pam3Csk4 stimulated goblet cell hyperplasia in both genotypes. Pam3Csk4 stimulation of goblet cell numbers was associated with suppression of Notch1 and Neurog3 expression and upregulated determinants of goblet cell differentiation. We conclude that goblet cell hyperplasia and inflammation of the Cftr KO small intestine are not exhibited by enteroids, indicating that this manifestation of CF intestinal disease is not epithelial-automatous but secondary to the altered CF intestinal environment.

Impairment of TGF-β signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice

2003 ◽  
Vol 284 (3) ◽  
pp. G525-G535 ◽  
Author(s):  
Christoph Schramm ◽  
Martina Protschka ◽  
Heinz H. Köhler ◽  
Jürgen Podlech ◽  
Matthias J. Reddehase ◽  
...  
Keyword(s):  
T Cells ◽  
Transgenic Mice ◽  
Autoimmune Hepatitis ◽  
Mononuclear Cells ◽  
Dominant Negative ◽  
Wild Type ◽  
Histological Score ◽  
Tgf Β1 ◽  
Increased Susceptibility ◽  
Experimental Autoimmune

In autoimmune hepatitis, strong TGF-β1 expression is found in the inflamed liver. TGF-β overexpression may be part of a regulatory immune response attempting to suppress autoreactive T cells. To test this hypothesis, we determined whether impairment of TGF-β signaling in T cells leads to increased susceptibility to experimental autoimmune hepatitis (EAH). Transgenic mice of strain FVB/N were generated expressing a dominant-negative TGF-β type II receptor in T cells under the control of the human CD2 promoter/locus control region. On induction of EAH, transgenic mice showed markedly increased portal and periportal leukocytic infiltrations with hepatocellular necroses compared with wild-type mice (median histological score = 1.8 ± 0.26 vs. 0.75 ± 0.09 in wild-type mice; P < 0.01). Increased IFN-γ production (118 vs. 45 ng/ml) and less IL-4 production (341 vs. 1,256 pg/ml) by mononuclear cells isolated from transgenic livers was seen. Impairment of TGF-β signaling in T cells therefore leads to increased susceptibility to EAH in mice. This suggests an important role for TGF-β in immune homeostasis in the liver and may teleologically explain TGF-β upregulation in response to T cell-mediated liver injury.

A thermal injury-induced circulating factor(s) compromises intestinal cell morphology, proliferation, and migration

1999 ◽  
Vol 277 (1) ◽  
pp. G175-G182 ◽  
Author(s):  
Maryam Varedi ◽  
George H. Greeley ◽  
David N. Herndon ◽  
Ella W. Englander
Keyword(s):  
Epithelial Cells ◽  
Thermal Injury ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Rat Serum ◽  
In Vitro Effects ◽  
Mucosal Morphology ◽  
And Migration

The effects of a 60% body surface area thermal injury in rats on the morphology and proliferation of the epithelium of the small intestine and the in vitro effects of serum collected from scalded rats on intestinal epithelial cells were investigated. Scald injury caused significant reductions in duodenal villus width and crypt dimensions, villus enterocytes changed in shape from columnar to cuboidal, and the number of goblet cells decreased. The proportion of bromodeoxyuridine-labeled S phase cells in crypts was also diminished. In vitro, incubation of intestinal epithelial cells (IEC-6) with scalded rat serum (SRS) collected at either 12 or 24 h after injury caused a disruption in the integrity of the confluent culture and induced the appearance of large denuded areas. SRS also decreased DNA synthesis and delayed wound closure in an in vitro wound-healing model. The thermal injury-induced changes in intestinal mucosal morphology and epithelial cell growth characteristics described in this study may underlie, in part, the mechanism(s) involved in the diminished absorption of nutrients, increased intestinal permeability, and sepsis in patients with thermal injury.

scholarly journals Peri-implant cartilage and bone histological changes following treatment of focal osteochondral defects in the femoral head with polyether ether ketone implants versus cobalt chromium molybdenum alloy implants: assessment in a goat model

2020 ◽  
Author(s):  
Zhiguo Yuan ◽  
Wei Zhang ◽  
Xiangchao Meng ◽  
Jue Zhang ◽  
Teng TengLong ◽  
...  
Keyword(s):  
Femoral Head ◽  
Osteochondral Defect ◽  
Osteochondral Defects ◽  
Cobalt Chromium ◽  
Cocrmo Alloy ◽  
Polyether Ether Ketone ◽  
Histological Score ◽  
Ether Ketone ◽  
Cobalt Chromium Molybdenum

Abstract Objective: This study aimed to quantitatively investigate the peri-implant histology of applying defect-size polyether ether ketone (PEEK) implant for the treatment of localized osteochondral defects in the femoral head and compared it with cobalt chromium molybdenum (CoCrMo) alloy implant.Methods: A femoral head osteochondral defect model was created in the left hips of goats (n=12). Defects were randomly treated by immediate placement of a PEEK (n=6) or CoCrMo implant (n=6). The un-operated right hip joints served as a control. Goats were sacrificed at 12 weeks. Periprosthetic cartilage quality was semi-quantitatively analyzed macroscopically and microscopically. Implant osseointegration was measured by micro-CT and histomorphometry.Results: The modified macroscopic articular evaluation score in the PEEK group was lower than that in the CoCrMo group (p<0.05), and the histological score of the periprosthetic and acetabular cartilage in the PEEK group was lower than that in the CoCrMo group (P<0.05). The mean bone-implant contact for PEEK implants was comparable with that for CoCrMo alloy implants at 12 weeks.Conclusions: A PEEK implant for the treatment of local osteochondral defect in the femoral head demonstrated effective fixation and superior in vivo cartilage protection compared with an identical CoCrMo alloy implant.

scholarly journals The challenge of ovarian tissue culture: 2D versus 3D culture

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ana Sofia Pais ◽  
Sandra Reis ◽  
Mafalda Laranjo ◽  
Francisco Caramelo ◽  
Fátima Silva ◽  
...  
Keyword(s):  
Tissue Culture ◽  
3D Model ◽  
Tissue Injury ◽  
Ovarian Tissue ◽  
Three Dimensional ◽  
3D Culture ◽  
Endocrine Function ◽  
Histological Score ◽  
Score Analysis ◽  
Alginate Matrix

Abstract Background Cryopreservation of ovarian tissue is a powerful technique for preserving female fertility, as it can restore fertility and endocrine function. To increase the longevity of the transplant and decrease the risk of reimplantation of neoplastic cells, several studies have been carried out with culture of ovarian tissue. The aim of this study was to compare a conventional (2D) culture with an alginate matrix three-dimensional (3D) model for ovarian tissue culture. Results The ovarian tissue culture within the alginate matrix (3D) was similar to 2D culture, regarding follicular density and cell apoptosis in follicles and stroma. The proliferation rate remained stable in both models for follicles, but for stromal cell proliferation it decreased only in 3D culture (p = 0.001). At 24 h of culture, cytotoxicity was lower in the 3D model (p = 0.006). As culture time increased, cytotoxicity seemed similar. Degradation of the tissue was suggested by the histological score analysis of tissue morphology after 72 h of culture. Tissue injury was greater (p = 0.01) in 3D culture due to higher interstitial oedema (p = 0.017) and tissue necrosis (p = 0.035). Conclusion According to our results, 3D culture of ovarian tissue has no advantage over 2Dculture; it is more time consuming and difficult to perform and has worse reproducibility.

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