The present study aimed to investigate the relationship between the disturbed balance of CD4+/CD8+, Th17/Treg and the activation of the Notch signaling pathway in experimental autoimmune uveitis (EAU).
Methods
An EAU rat model was induced in Lewis rats, and pathology analysis was performed by hematoxylin and eosin (H&E) staining. CD4+, CD8+, Th17, and Treg levels in spleen, lymph nodes and eye tissues were determined by flow cytometry. Meanwhile, the expression of Notch1, DLL4, IL-10, and IL-17 was determined by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the inhibitory effect of N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT) on Th17 differentiation by Notch signaling in vitro was further investigated using T lymphocytes from EAU rats on day 12 post-immunization by flow cytometry.
Results
The pathological results showed that inflammatory cell infiltration occurred in ocular tissues in EAU rats. The CD4+/CD8+ and Th17/Treg ratios in EAU rats were apparently higher than those in normal control individuals. Q-PCR and ELISA analyses indicated the expression of Notch1, DLL4, IL-10, and IL-17 in EAU rats gradually increased on day 6 after immunization, peaked on day 12, and then gradually decreased. The dynamic trends in Notch1 and DLL4 expression in EAU rats were identical to those of CD4+/CD8+ and Th17/Treg levels. DAPT can significantly inhibit the activation of Notch signaling, decrease Th17 cell differentiation, and attenuate the level of the Th17 cell lineage, contributing to the balance of the Th17/Treg ratio.
Conclusion
The activation of the Notch signaling pathway can regulate Th17 and Treg cell differentiation, disrupt the CD4+/CD8+ and Th17/Treg balance, and aggravate the severity of EAU; inactivation of the Notch signaling pathway contributes to the CD4+/CD8+ and Th17/Treg balance in EAU rats. Our findings highlighted that the dynamic change in the CD4+/CD8+ and Th17/Treg ratio was consistent with the expression trend of Notch signaling in EAU rats, suggesting that Notch signaling may be a potentially important therapeutic target in clinical practice.
The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair
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The biodegradability of water-extracted saponins of berries from the Endod plant, Phytolacca dodecandra L'Herit, was evaluated under OECD standardized conditions. Persistence of the saponins was evaluated by determination of saponin concentrations in water over a 30-day period, using a quantitative HPLC method and a semiquantitative hemolytic assay, which is considered a potential field method. The two methods were compared. Bioassays were simultaneously conducted using Biomphalaria glabrata fresh water snails to assess the molluscicidal potency over time. All experiments were carried out in water, which was chemically balanced to sustain snails, and to one set river water was added to the medium to mimic natural conditions. (1) Saponin concentrations in water treated with an aqueous extract of P. dodecandra cultivar E44 were stable for 2 days then rapidly decreased during the third and fourth day. Lethal concentrations to snails were LC50 = 9.6 mg/l (95% CI: 6.3 to 19.4) in one set and LC50 = 6.8 mg/l (95% CI: 5.4 to 12.2) in the other. Adding river water to one set of the experiments had no effect on the mean saponin concentration over time (F = 0.02, P = >0.05). (2) Comparison of the hemolytic assay with the HPLC method showed no significant difference in mean saponin concentrations (t = 0.32, P > 0.05, 95% CI: -2.67 to 3.64), and a correlation of r2 = 0.88 between the two methods. (3) The saponin fraction of an aqueous extract of P. dodecandra was readily biodegraded (t1/2 = 15.8 h), and the complete consumption within a 10-day window indicates ready degradability in aquatic environments under aerobic conditions. (4) These results show that the use of Endod berries for snail control in schistosomiasis-infested water bodies is environmentally acceptable. 相似文献