scholarly journals Inside Front Cover: Genistein Inhibits Colonic Goblet Cell Loss and Colorectal Inflammation Induced by Salmonella Typhimurium Infection

2021 ◽  
Vol 65 (16) ◽  
pp. 2170041
Author(s):  
Yang He ◽  
Hammed Ayansola ◽  
Qihang Hou ◽  
Chaoyong Liao ◽  
Jiaqi Lei ◽  
...  
2021 ◽  
pp. 2100209
Author(s):  
Yang He ◽  
Hammed Ayansola ◽  
Qihang Hou ◽  
Chaoyong Liao ◽  
Jiaqi Lei ◽  
...  

2020 ◽  
Vol 21 (23) ◽  
pp. 8890
Author(s):  
Claudia M. Trujillo-Vargas ◽  
Shallu Kutlehria ◽  
Humberto Hernandez ◽  
Rodrigo G. de Souza ◽  
Andrea Lee ◽  
...  

Dry eye disease (DED), one of the most prevalent conditions among the elderly, is a chronic inflammatory disorder that disrupts tear film stability and causes ocular surface damage. Aged C57BL/6J mice spontaneously develop DED. Rapamycin is a potent immunosuppressant that prolongs the lifespan of several species. Here, we compared the effects of daily instillation of eyedrops containing rapamycin or empty micelles for three months on the aged mice. Tear cytokine/chemokine profile showed a pronounced increase in vascular endothelial cell growth factor-A (VEGF-A) and a trend towards decreased concentration of Interferon gamma (IFN)-γ in rapamycin-treated groups. A significant decrease in inflammatory markers in the lacrimal gland was also evident (IFN-γ, IL-12, CIITA and Ctss); this was accompanied by slightly diminished Unc-51 Like Autophagy Activating Kinase 1 (ULK1) transcripts. In the lacrimal gland and draining lymph nodes, we also observed a significant increase in the CD45+CD4+Foxp3+ cells in the rapamycin-treated mice. More importantly, rapamycin eyedrops increased conjunctival goblet cell density and area compared to the empty micelles. Taken together, evidence from these studies indicates that topical rapamycin has therapeutic efficacy for age-associated ocular surface inflammation and goblet cell loss and opens the venue for new investigations on its role in the aging process of the eye.


2018 ◽  
Vol 24 (3) ◽  
pp. S169-S170 ◽  
Author(s):  
Takahide Ara ◽  
Daigo Hashimoto ◽  
Eiko Hayase ◽  
Clara Noizat ◽  
Kana Matsuda ◽  
...  

2015 ◽  
Vol 56 (12) ◽  
pp. 7545 ◽  
Author(s):  
Stephen C. Pflugfelder ◽  
Cintia S. De Paiva ◽  
Quianta L. Moore ◽  
Eugene A. Volpe ◽  
De-Quan Li ◽  
...  
Keyword(s):  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4491-4491
Author(s):  
Pritesh R. Patel ◽  
Sonal Ghandi ◽  
Snehal Sonawane ◽  
Sapna Tibrewal ◽  
Saumad Jassim ◽  
...  

Abstract Abstract 4491 The treatment of chronic ocular graft-versus-host disease (GVHD) is empirical, mainly due to the lack of knowledge of its pathogenesis. The goals of this study were to describe the histopathologic and immunophenotypic characteristics of conjunctival biopsies from patients with chronic ocular GVHD and to determine whether these findings can guide immunomodulation or palliative management strategies of GVHD associated dry eye disease. A conjuctival biopsy was obtained in eleven patients who previously received an allogeneic hematopoietic stem cell transplant (HSCT) and presented with chronic GVHD and dry eye symptoms. Hematoxylin and eosin (H&E) and immunohistochemical staining of conjunctival biopsies were analyzed for presence of inflammatory cells (B and T cells), fibrosis, and apoptosis. All conjunctival biopsies showed the presence of keratosis and parakeratosis and 7/11 (64%) biopsies had evidence of conjunctival epithelial apoptosis. Immunohistochemistry demonstrated the presence of inflammatory cells in 72% (8/11). These cells were predominantly CD3+ T lymphocytes (54%), with a CD4:CD8 cell ratio of 1:1.7. No biopsies showed B cells. Fibrosis was noted in 54% of biopsies (6/11). Conjunctival apoptosis detected by caspase-3 antibody staining showed significant moderate positive correlation with goblet cell loss (r=0.6, p=0.04). Presence of inflammatory cells showed a stronger correlation with conjunctival apoptosis as compared with fibrosis (r=0.38 and 0.26 respectively), however both correlations were not significant (p<0.05). A standard dry eye treatment regimen in chronic ocular GVHD remains to be determined, thus examining the histopathologic features may help guide a more focused management strategy. In this study conjunctival apoptosis was associated with significant goblet cell loss and it more frequently accompanied inflammation as compared to fibrosis. Aggressive topical immunomodulation may reduce inflammation and goblet cell loss in patients with conjunctival biopsies positive for apoptosis. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 12 (550) ◽  
pp. eaaw0720
Author(s):  
Takahide Ara ◽  
Daigo Hashimoto ◽  
Eiko Hayase ◽  
Clara Noizat ◽  
Ryo Kikuchi ◽  
...  

Graft-versus-host disease (GVHD) and infection are major obstacles to successful allogeneic hematopoietic stem cell transplantation (HSCT). Intestinal goblet cells form the mucus layers, which spatially segregate gut microbiota from host tissues. Although it is well known that goblet cell loss is one of the histologic features of GVHD, effects of their loss in pathophysiology of GVHD remain to be elucidated. In mouse models of allogeneic HSCT, goblet cells in the colon were significantly reduced, resulting in disruption of the inner mucus layer of the colon and increased bacterial translocation into colonic mucosa. Pretransplant administration of interleukin-25 (IL-25), a growth factor for goblet cells, protected goblet cells against GVHD, prevented bacterial translocation, reduced plasma concentrations of interferon-γ (IFN-γ) and IL-6, and ameliorated GVHD. The protective role of IL-25 was dependent on Lypd8, an antimicrobial molecule produced by enterocytes in the colon that suppresses motility of flagellated bacteria. In clinical colon biopsies, low numbers of goblet cells were significantly associated with severe intestinal GVHD, increased transplant-related mortality, and poor survival after HSCT. Goblet cell loss is associated with poor transplant outcome, and administration of IL-25 represents an adjunct therapeutic strategy for GVHD by protecting goblet cells.


Cornea ◽  
1992 ◽  
Vol 11 (1) ◽  
pp. 41-43
Author(s):  
Karl G. Stonecipher ◽  
Grace Shin ◽  
Mike Pohlod ◽  
Dan Tepper ◽  
Zeynel A. Karcioglu ◽  
...  

2021 ◽  
Vol 22 (4) ◽  
pp. 1946
Author(s):  
Charlotte van Gorp ◽  
Ilse H. de Lange ◽  
Kimberly R. I. Massy ◽  
Lilian Kessels ◽  
Alan H. Jobe ◽  
...  

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d gestational age (GA). Gut inflammation, the number, distribution, and differentiation of goblet cells, ER stress, and apoptosis were measured. We found a biphasic reduction in goblet cell numbers 24 h–2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics.


Cornea ◽  
2012 ◽  
Vol 31 (11) ◽  
pp. 1299-1303 ◽  
Author(s):  
Cintia S. de Paiva ◽  
C. Eric Schwartz ◽  
Per Gjörstrup ◽  
Stephen C. Pflugfelder

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