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Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.

Introduction During the past decade, nonoperative management (NOM) for simple acute appendicitis (SAA) in children has been proven safe with noninferior complications rate. The aim of this study was to examine Alvarado score and pediatric appendicitis score (PAS) together with other factors in predicting failure of NOM in children presenting with SAA. Materials and Methods Patients aged 5 to 18 years admitted to our department between 2017 and 2019 diagnosed with SAA were given a choice between surgical management and NOM. We divided the NOM patients into two groups: successful treatment and failed NOM, comparing their files for Alvarado score and PAS and other clinical and demographic factors, with a mean follow-up of 7 months. Failure was determined as need for appendectomy following conservative treatment due to any reason. Results A total of 85 patients answered criteria and chose NOM. Overall failure rate was 32.9%. We found no difference in the mean Alvarado score and PAS as well as in each component of both scores between success and failed NOM groups. However, when using the risk classification of the scores, we found a significant correlation between high-risk Alvarado score and failed NOM. After adjusting for age, gender, duration of symptoms, diagnosis of tip appendicitis, and presence of appendicolith, the odds of failure were four times higher among high-risk Alvarado group. Conclusion Alvarado score of 7 or higher, older age, and diagnosis of an appendicolith on imaging are possible predictors for failure of NOM for SAA in children.

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