Direct interference with Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has recently been introduced as an attractive approach to control life-threatening diseases like myocarditis. The present study aimed to investigate the potential application in myocarditis of a series of novel non-naphthalene derivatives as potential Keap1-Nrf2 PPI inhibitors. Our results indicated that the optimal compound K22 displayed the highest metabolic stability and showed notable Keap1-Nrf2 PPI inhibitory activities in vitro . K22 effectively triggered Nrf2 activation and increased the protein and mRNA expression of Nrf2-regulated genes in H9c2 cells. Moreover, pre-treatment with K22 was shown to mitigate LPS-induced damage to H9c2 cells, causing a marked decrease in the levels of inflammatory factors as well as reactive oxygen species (ROS). Furthermore, K22 was also shown to be non-mutagenic in the Ames test. Overall, our findings suggest that K22 may be a promising drug lead as a Keap1-Nrf2 PPI inhibitor for myocarditis treatment.

Background. Tendinopathy is a disabling musculoskeletal disorder affecting the athletics and general populations. There have been increased studies using stem cells in treating tendon diseases. The aim of this bibliometric and visualized study is to comprehensively investigate the current status and global trends of research in tendon stem cells. Methods. Publications related to tendon stem cells from 1991 to 2020 were retrieved from Web of Science and then indexed using a bibliometric methodology. VOSviewer software was used to conduct the visualized study, including coauthorship, cocitation, and cooccurrence analysis and to analyze the publication trends of research in tendon stem cells. Results. In total, 2492 articles were included and the number of publications increased annually worldwide. The United States made the largest contribution to this field, with the most publications (938 papers, 37.64%), citation frequency (68,195 times), and the highest H -index (103). The most contributive institutions were University of Pittsburgh (96 papers), Zhejiang University (70 papers), Shanghai Jiao Tong University, and Chinese University of Hong Kong (both 64 papers). The Journal of Orthopaedic Research published the most relative articles. Studies could be classified into five clusters: “Animal study,” “Tissue engineering,” “Clinical study,” “Mechanism research,” and “Stem cells research”, which show a balanced development trend. Conclusion. Publications on tendon stem cells may reached a platform based on current global trends. According to the inherent changes of hotspots in each cluster and the possibilities of cross-research, the research in tendon stem cells may exist a balanced development trend.

Background: The change in hip-knee-ankle (HKA) angle after total knee arthroplasty (TKA) may cause an adjustment in hindfoot alignment (HFA). However, the relationship between the changes in HKA angle and HFA is still not well studied. This study aimed to investigate the association between HKA angle and hindfoot alignment changes after TKA for varus knee osteoarthritis.Methods: A prospective study was carried out in which 108 patients with varus knee deformities were radiographically and clinically evaluated before and 3 months after TKA. The relationship of change in HFA with correction in HKA angle was investigated.Results: The results showed that the HFA was adjusted significantly by 3 months after TKA (p < 0.001), along with improved American Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot score (p < 0.001). Next, a univariate correlation and linear regression analysis showed that the change in HFA was weakly correlated with the change in HKA angle (r=-0.262, β=-0.14, 95% CI: -0.23 to -0.04, P=0.006). Further stratified analysis and interaction tests revealed that age has a distinct effect on the correlation between the changes in HFA and HKA angle. The correlation was dramatically greater in the group under 65 years (r=-0.474, β=-0.26, 95% CI: -0.41 to -0.12, P=0.001), whilst, no correlation was observed in those above 65 years old (r=-0.036, β=-0.02, 95% CI: -0.14 to 0.11, P=0.779). Conclusion: Our findings indicated that correction of HKA after TKA tend to promote adjustment in the hindfoot alignment toward re-balance of the whole lower limb weight-bearing axis. However, this mechanism obviously weakens in elderly patients. Therefore, if apparent hindfoot deformity exists in these patients before TKA, more perioperative intervention is required for hindfoot adjustment, and even HKA undercorrection may be considered.

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