BACKGROUND AND PURPOSEKaempferol, a dietary flavonoid and phyto-oestrogen, is known to have anti-inflammatory properties. Microglial activation has been implicated in various neurodegenerative diseases. Anti-inflammatory effects of kaempferol and the underlying mechanisms were investigated by using LPS-stimulated microglial BV2 cells. EXPERIMENTAL APPROACHCell viability was measured using MTT and neutral red assays. ELISA, Western blot, immunocytochemistry and electrophoretic mobility-shift assay were used to analyse NO, PGE2, TNF-a and IL-1b production, inducible NOS (iNOS), COX-2 expression and the involvement of signalling pathways such as toll-like receptor-4 (TLR4), MAPK cascades, PKB (AKT) and NF-kB. Accumulation of reaction oxygen species (ROS) was measured by nitroblue tetrazolium and 2′7′-dichlorofluorescein diacetate assay. Matrix metalloproteinase activity was investigated by zymography and immunoblot assay. Phagocytotic activity was assessed by use of latex beads. KEY RESULTSKaempferol significantly attenuated LPS-induced NO, PGE2, TNF-a, IL-1b and ROS production and phagocytosis in a concentration-dependent manner. Kaempferol suppressed the expression of iNOS, COX-2, MMP-3 and blocked the TLR4 activation. Moreover, kaempferol inhibited LPS-induced NF-kB activation and p38 MAPK, JNK and AKT phosphorylation. CONCLUSION AND IMPLICATIONSKaempferol was able to reduce LPS-induced inflammatory mediators through the down-regulation of TLR4, NF-kB, p38 MAPK, JNK and AKT suggesting that kaempferol has therapeutic potential for the treatment of neuroinflammatory diseases. AbbreviationsAKT, PKB; iNOS, inducible NOS; ROS, reactive oxygen species; TLR-4, toll-like receptor-4 (TLR4) BJP British Journal of Pharmacology

Background Peri-appendiceal inflammation (PAI) is often found in patients with left-sided ulcerative colitis (UC) or proctitis. However, there is still no consensus on the clinical significance of PAI. This study aimed to identify the clinical significance of PAI in UC as a prognosis factor. Methods We retrospectively collected medical records and endoscopic results of patients with diagnosed left side UC or proctitis between January 2013 and December 2021. According to the presence of PAI, we divided the patients into PAI and non-PAI groups. Demographic features and clinical course of the two groups were collected and analyzed. Results A total of 107 patients (41 of left site UC, 56 of proctitis) were enrolled, of which 52 were in the PAI group and 55 were in the non-PAI group There was no difference in most of the demographic and clinical variables between the PAI and non-PAI groups. During the follow-up period of 51 months for the PAI group and 46 months for the non-PAI group, respectively, there was no difference in disease relapse rate (47.1% vs 49.1%, p=0.823), cumulative rate of disease relapse at 1, 3, and 5 years (10.7%, 26.2%, 34.8% vs 8.39%, 23.0%, 36.7%, p=0.823), rate of treatment escalation (59.6% vs 41.8%, p=0.066) and proximal disease extension (25% vs 25.5%, p=0.957) however, new occurrence of PAI during the follow-up period in the non-PAI group was associated with proximal disease extension (55.6% vs 19.6%, p=0.037) In this study, oral 5-aminosalicylate (ASA) was administered to most patients regardless of the extent of the disease. In patients with proctitis with PAI, oral 5-ASA did not affect relapse rate (37.1% vs 66.7%, p=0.550) and proximal disease extension rate (28.6% vs 33.3%, p=1.000). Conclusion PAI at diagnosis did not affect the course of the disease nor did oral 5-ASA in proctitis, however new occurrences of PAI during follow-up were associated with proximal disease extension.

Background Biologics such as infliximab is the main treatment for steroid refractory acute severe ulcerative colitis (ASUC), However, there are only a few studies on the effectiveness and safety of biologics in steroid refractory ASUC. In this study, we evaluated the effectiveness and safety of biologics as a rescue therapy for biologics naïve steroid refractory ASUC patient in Korea. Methods We retrospectively included patients who were hospitalized at seven tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the demographic and clinical variables, disease activity, treatment method, treatment response, adverse event, readmission due to any reasons were checked Results A total of 230 ASUC patients were included, of which 220 were biologic naïve patient. The response rate of steroid in these patients was 74%, and infliximab was administered as rescue therapy to 53 patients who failed initial steroid treatment. The response rate to infliximab as rescue therapy was 96%, and 2 patients who did not respond received colectomy. One of the two patients who underwent colectomy died of sepsis. There was no infliximab-related adverse event during hospitalization. Although infliximab itself was not a factor associated with infection after discharge (10% vs. 16%, p=0.355), combination therapy with thiopurine was a risk factor for infection after discharge. (Odd ratio 7.302, 95% CI 2.101-25.372, p=0.002). A total of 12 infections occurred in patients treated with infliximab after discharge (3 pneumonia, 1 skin infection, 3 cytomegalovirus colitis, 4 Clostridium difficile infection) and were associated with readmission. (40.1% vs. 75%, p=0.031) Conclusion As a rescue therapy in biologics naive steroid refractory ASUC, infliximab showed a 96% therapeutic response. Although infliximab itself did not increase the risk of infection after discharge, the combination with thiopurine increased the risk of infection after discharge