Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

The treatment of inflammatory bowel disease with monoclonal antibodies in Asia.

Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), are chronic, systemic autoimmune diseases. As the incidence of IBD rapidly increases in Asia, increasing attention has been paid to developing additional treatment strategies. Presently, the end point of therapy is achieving clinical and endoscopic remission through the blockade of inflammatory cascades. Recent studies have shown that monoclonal antibodies (mAbs) use for precise molecular targeting of inflammatory pathways has a promising effect on IBD, especially moderate-to-severe CD and UC. Since the 1997 report on the use of infliximab (a monoclonal antibody against tumor necrosis factor alpha [TNF-α]) in patients with CD, mAbs have expanded therapeutic options and have also complicated initial management options and subsequent treatment. This review comprehensively summarizes the clinical reports and studies related to the use of mAbs for the treatment of IBD in Asian countries and regions in recent years thus demonstrating the current status of mAbs use in Asia. In addition, the differences in the use of mAbs for the treatment of IBD between the Asia and the West are expounded. Ultimately, it is hoped that this review will provide new insights and a scientific basis for the clinical application of mAbs.

Biomechanical and clinical evaluation of interlocking hip screw in Pauwels â ¢ femoral neck fractures: A comparison with inverted triangle cannulated screws.

Purpose: To compare biomechanical and clinical properties of the novel internal fixation Interlocking Hip Screw (IHS) and conventional inverted triangle cannulated screws (ITCS) for treatment of Pauwels Ⅲ femoral neck fractures. Methods: Twenty synthetic femurs were osteotomized to simulate 70° Pauwels Ⅲ femoral neck fractures and randomly divided into two groups: Group IHS and Group ITCS. Specimens were loaded in quasi-static ramped and cyclical compression testing in 25° adduction to analyze for axial stiffness, failure load, and interfragmentary displacement. 21 matched patients with Pauwels Ⅲ femoral neck fracture who received closed reduction and internal fixation from January 2020 to January 2021 in both Group IHS and Group ITCS. Demographic data, time to surgery, operating duration, intraoperative blood loss, number of fluoroscopies, length of hospital stay, fracture healing time, Harris Hip Score (HHS), the score of Visual Analogue Scale (VAS) and complications such as nonunion, avascular necrosis, and femoral neck shortening were compared. Results: All specimens in the two groups survived in the axial and cyclical compression test. The axial stiffness was significantly higher for Group IHS (277.80 ± 26.58 N/mm) versus Group ITCS (205.33 ± 10.46 N/mm), p < 0.05. The maximum failure loading in Group IHS performed significantly higher than in Group ITCS (1,400.48 ± 71.60 N versus 996.76 ± 49.73 N, p < 0.05). The interfragmentary displacement of the cyclic loading test for Groups IHS and Group ITCS was 1.15 ± 0.11 mm and 1.89 ± 0.14 mm, respectively, p < 0.05. No significant difference was found in terms of demographic data, time to surgery, intraoperative blood loss, length of hospital stay and the occurrence of nonunion and avascular necrosis between groups. Shorter operating duration and fewer intraoperative fluoroscopic views were noticed using IHS compare to ITCS, p < 0.05. The HHS was 72.14 ± 5.76 and 86.62 ± 5.01 in Group IHS, and was 67.29 ± 5.27 and 81.76 ± 5.13 in Group ITCS at 3-month and 6-month follow-up, respectively, p < 0.05. The magnitude of femoral neck shortening was significantly lower in Group IHS compared to Group ITCS (4.80 ± 1.03 mm versus 5.56 ± 1.21 mm, p < 0.05). Conclusion: Our study demonstrated that IHS provided better biomechanical and clinical performance due to its unique biological and biomechanical mechanisms, compared with ITCS. Thus, IHS is a feasible alternative to ITCS for the fixation of Pauwels Ⅲ femoral neck fractures.