Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1β) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.

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Background and Aim The incidence of nonalcoholic fatty liver disease (NAFLD) as a metabolic disease is increasing annually. In the present study, we aimed to explore the influence of NAFLD on the severity of acute pancreatitis (AP). Methods The severity of AP was diagnosed and analyzed according to the 2012 revised Atlanta Classification. Outcome variables, including the severity of AP, organ failure (all types of organ failure), and systemic inflammatory response syndrome (SIRS), were compared for patients with and without NAFLD. Results Six hundred and fifty-six patients were enrolled in the study and were divided into two groups according to the presence or absence of NAFLD. The non-NAFLD group contained 278 patients and the main etiology in this group was gallstone. The NAFLD group consisted of 378 patients and the main etiology was hyperlipidemia. The incidence of mild AP, moderately severe AP, and severe AP was 77.30%, 18.3%, and 4.3% in the non-NAFLD group and 58.2%, 33.9%, and 7.9% in the NAFLD group, respectively. There were significant differences between the two groups according to the severity of AP (P ≤ 0.001). In addition, the Ranson and BISAP scores as well as the incidence of SIRS and organ failure in the NAFLD group were higher than those in the non-NAFLD group (all P < 0.05). The patients were further divided into non-NAFLD, mild-NAFLD, and moderate-severe NAFLD (M+S-NAFLD) groups. The results showed that the severity of AP increased gradually from the non-NAFLD group to the M+S-NAFLD group. In addition, the incidence rates of SIRS and organ failure showed an upward trend with the aggravation of fatty liver severity. Multivariate logistic analysis showed that patients with NAFLD, especially those with M+S-NAFLD, had higher risks of SIRS and organ failure. Conclusions Compared with non-NAFLD, NAFLD has a clinically relevant impact on the severity of AP and may be an early prognostic parameter for patients with AP.

Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.