The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.

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Aim: To evaluate the analgesic effects of 2 celecoxib derivatives and their inhibitory effects on cyclooxygenase (COX). Methods: Four antinociceptive assays were used: the acetic acid-induced writhing test, hot plate test, hot tail-flick test and formalin test. Three doses were used in the analgesic assays and ED 50 values were calculated. For the selectivity assay, macrophages were incubated with test compounds at various concentrations and then stimulated with calcimycin or lipopolysaccharide (LPS). The amounts of 6-keto-prostaglandin F 1α (6-keto-PGF 1α ) and prostaglandin E 2 (PGE 2 ) in the supernatant were examined by radioimmunoassay (RIA). The selectivity of the test compounds was expressed as the IC 50,COX-1 / IC 50,COX-2 value. Results: Celecoxib and its 2 derivatives had a significant analgesic effect. The ED 50 values of celecoxib, PC-406 and PC-407 were 94.2, 67.9, and 63.3 mg/kg, respectively, for the acetic acid-induced writhing test; 104.7, 89.1, and 30.0 mg/kg, respectively, for the hot tail-flick response test; 60.7, 56.7, and 86.2 mg/kg, respectively, for the hot plate response test; 67.1, 55.8, and 68.8 mg/kg, respectively, for the formalin-induced response. That is, the ED 50 of PC-406 was the lowest for the formalin and hot plate tests, which focus on changes above the spinal cord level; however, the ED 50 of PC-407 was lowest for the tail-flick and writhing tests, which focus on changes at the spinal cord level. Celecoxib and PC-407 inhibited COX-1 with IC 50 values of 39.8 and 27.5 nmol/L, respectively. PC-406 inhibited COX-1 with an IC 50 value of more than 1000 nmol/L. The IC 50 values for the effect of celecoxib, PC-406 and PC-407 on COX-2 were 4.8, 8.9, and 1.9 nmol/L respectively. The IC 50,COX-1 /IC 50,COX-2 ratios for celecoxib and PC-407 were 8.3 and 14.4, respectively. For PC-406, the ratio was greater than 112.2. Conclusion: Derivatives of celecoxib via substitution with an isopropyl or naphthyl group at the 5 position in the pyrazole ring still have analgesic effects and the ability to selectively inhibit COX-2. Substitution with a naphthyl group may have more effect on the peripheral pain pathway, whereas substitution with an isopropyl group may have more effect on the central pain pathway. This phenomenon occurs partly because substitution with an isopropyl group is more beneficial for COX-2 selectivity than is substitution with a naphthyl group.

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