NF-κB pathway.docx

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1、The Lycium barbarum polysaccharide protects corneal epithelial cells under high glucose via IKKp/NF-kB pathwayDiscussionThere is no effective treatment for diabetic keratopathy so far. Patients with diabetic keratopathy often have symptoms such as congestion and edema15J. Studies have found that man

2、nitol can not only be used as an osmotic pressure regulator to relieve eye swelling, but also scavenge free radicals and reduce inflammation 16, 17. Therefore, mannitol is commonly used in clinical adjuvant treatment of diabetic keratopathy 18. This study is the first to propose the protective effec

3、t of LBP on the injured HCECs induced by high glucose. We found that 200 pg/mL LBP had a significant repairing effect on the injury of HCECs induced by high glucose, and the effect was only slightly worse than that of 75mM mannitol.LBP, as an active ingredient of Traditional Chinese medicine Lyciutn

4、 barharuni, has been found to play an important role in improving eye diseases in recent years19, 20. Liu et al. proposed that LBP activated PI3K/AKT and ERK signaling pathways by upregulating miR-4295, thereby alleviating FhCh-induced injury of human trabecular reticular cells19. Mi and colleagues

5、found that LBP protected retinal ganglion cells by reducing the expression of endothelin-1 and its receptors ETA and ETB in chronic ocular hypertension rats20J. In this study, we found that LBP could inhibit the apoptosis of injured HCECs and reduce the level of oxidative stress and inflammatory res

6、ponse, which may be achieved by inhibiting the IKKVNF-kB pathway. Transcription factor NF-kB is an important inflammatory regulator, involved in inflammatory and immune responses, cell cycle regulation and other processes21 . In the absence of external stimulation, NF-kB binds to its inhibitor IkB i

7、n the cytoplasm21. IKK。is a kinase of IkB, which can phosphorylate and degrade IkB, thereby activating the activity of NF-kB22J. NF-kB has been found to induce inflammatory responses and apoptosis in many chronic diseases23-25J. In this study, although we found that the expression of IKK。and NF-kB P

8、65 was significantly decreased in the injured HCECs after treatment with LBP, more rigorous experiments are needed to verify the correlation between IKK0/NF-kB pathway and the protective effect on HCECs.In conclusion, this study confirmed the protective effect of LBP on HCECs injured by high glucose

9、. LBP inhibits the apoptosis of injured HCECs and reduces levels of oxidative stress and inflammatory response, possibly by inhibiting the IKK0/NF-kB pathway. Our study provides a theoretical basis for the application of LBP in the improvement of diabetic keratopathy.ReferencesCole JB, Florez JC. Ge

10、netics of diabetes mellitus and diabetes complications. Nature reviews nephrology. 2020;16(7):377-90.1 Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62(l):3-16.2 Berrocal MH, Acaba LA, Acaba A. Surgery

11、 for diabetic eye complications. Current diabetes reports, 2016:16(10):1-7.3 Lu J, Sheng M, Yao P, Ran C, Liu H, Chen L, et al. High concentration of glucose increases reactive oxygen species generation and apoptosis induced by endoplasmic reticulum stress pathway in rabbit corneal epithelial cells.

12、 Journal of ophthalmology. 2018:2018.4 Goldstein AS, Janson BJ, Skeie JM, Ling JJ, Greiner MA. The effects of diabetes mellitus on the corneal endothelium: A review. Survey of ophthalmology. 2020:65(4):438-50.5 Di G, Zhao X, Qi X, Zhang S, Feng L, Shi W, et al. VEGF-B promotes recovery of corneal in

13、nervations and trophic functions in diabetic mice. Scientific reports. 2017;7(l):l-13.6 Li C, Gan H, Tan X, Hu 乙 Deng B, Sullivan MA, et al. Effects of active ingredients from traditional Chinese medicines on glycogen molecular structure in diabetic mice. European Polymer Journal, 2019;112:67-72.7 Z

14、hang T-T, Jiang J-G. Active ingredients of traditional Chinese medicine in the treatment of diabetes and diabetic complications. Expert opinion on investigational drugs. 2012;21(ll):1625- 42.8 Kwok SS, Bu Y, Lo AC-Y, Chan TC-Y, So KF, Lai JS-M. A systematic review of potential therapeutic use of Lyc

15、ium barbarum polysaccharides in disease. BioMed research international. 2019:2019.9 Deng X, Li X, Luo S, Zheng Y, Luo X, Zhou L. Antitumor activity of Lycium barbarum polysaccharides with different molecular weights: an in vitro and in vivo study. Food & nutrition research, 2017.10 Kwok SS, Wong FS-

16、Y, Chan Y-K, Bu Y, Chan TC-Y, Ng AL-K, et al. Lycium barbarum Polysaccharide Suppresses Expression of Fibrotic Proteins in Primary Human Corneal Fibroblasts. Journal of Clinical Medicine. 2020:9(11):3572.11 Pop C, Berce C, Ghibu S, Scurtu I, SoriQu O, Login C, et al. Effects of Lycium barbarum L. polysaccharides on inflammation and oxidative stress markers in a pressure overload-induced heart failure rat model. Molecules. 2020;

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