BACKGROUND AND PURPOSE Shogaols are reported to possess anti‐inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms.EXPERIMENTAL APPROACH The anti‐invasive effect of a series of shogaols was initially evaluated on MDA‐MB‐231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6‐shogaol on phorbol 12‐myristate 13‐acetate (PMA)‐induced matrix metalloproteinase‐9 (MMP‐9) gelatinolytic activity and nuclear factor‐κB (NF‐κB) activation were further determined.KEY RESULTS Shogaols (6‐, 8‐ and 10‐shogaol) inhibited PMA‐stimulated MDA‐MB‐231 cell invasion with an accompanying decrease in MMP‐9 secretion. 6‐Shogaol was identified to display the greatest anti‐invasive effect in association with a dose‐dependent reduction in MMP‐9 gene activation, protein expression and secretion. The NF‐κB transcriptional activity was decreased by 6‐shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF‐κB p65 phosphorylation and nuclear translocation. In addition, 6‐shogaol was found to inhibit JNK activation with no resulting reduction in activator protein‐1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF‐κB signalling, but not JNK and p38 signalling, were involved in PMA‐stimulated MMP‐9 activation.CONCLUSIONS AND IMPLICATIONS 6‐Shogaol is a potent inhibitor of MDA‐MB‐231 cell invasion, and the molecular mechanism involves at least in part the down‐regulation of MMP‐9 transcription by targeting the NF‐κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.

Background: Medication adherence is essential for improving the health outcomes of patients. Various patient-reported outcome measures (PROMs) have been developed to measure medication adherence in patients. However, no study has summarized the psychometric properties of these PROMs to guide selection for use in clinical practice or research. Objective: This study aims to evaluate the quality of the PROMs used to measure medication adherence. Methods: This study was guided by the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Relevant articles were retrieved from the EMBASE, PubMed, Cochrane Library, Web of Science, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases. The PROMs were then evaluated based on the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. Results: A total of 121 unique medication adherence PROMs from 214 studies were identified. Hypotheses testing for construct validity and internal consistency were the most frequently assessed measurement properties. PROMs with at least a moderate level of evidence for ≥5 measurement properties include the Adherence Starts with Knowledge 20, Compliance Questionnaire-Rheumatology, General Medication Adherence Scale, Hill-Bone Scale, Immunosuppressant Therapy Barrier Scale, Medication Adherence Reasons Scale (MAR-Scale) revised, 5-item Medication Adherence Rating Scale (MARS-5), 9-item MARS (MARS-9), 4-item Morisky Medication Adherence Scale (MMAS-4), 8-item MMAS (MMAS-8), Self-efficacy for Appropriate Medication Adherence Scale, Satisfaction with Iron Chelation Therapy, Test of Adherence to Inhalers, and questionnaire by Voils. The MAR-Scale revised, MMAS-4, and MMAS-8 have been administered electronically. Conclusions: This study identified 121 PROMs for medication adherence and provided synthesized evidence for the measurement properties of these PROMs. The findings from this study may assist clinicians and researchers in selecting suitable PROMs to assess medication adherence.

The role of thioredoxin reductase (TrxR) in tumorigenesis has made it an attractive anticancer target. A systematic approach for development of novel compounds as TrxR inhibitors is currently lacking. Structurally diversified TrxR inhibitors share in common electrophilic propensities for the sulfhydryl groups, among which include the Michael reaction acceptors containing an α,β-unsaturated carbonyl moiety. We aimed to identify features among structurally diversified Michael acceptor-based compounds that would yield a strong TrxR inhibitory character. Structurally dissimilar Michael acceptor-based natural compounds such as isobutylamides, zerumbone, and shogaols (SGs) were found to possess a poor TrxR inhibitory activity, indicating that a sole Michael acceptor moiety was insufficient to produce TrxR inhibition. The 1,7-diphenyl-hept-3-en-5-one pharmacophore in 3-phenyl-3-SG, a novel SG analog that possessed comparable TrxR inhibitory and antiproliferative potencies as 6-SG, was modified to yield 1,5-diphenyl-pent-1-en-3-one (DPPen) and 1,3-diphenyl-pro-1-en-3-one (DPPro, also known as chalcone) pharmacophores. These Michael acceptor-centric pharmacophores, when substituted with the hydroxyl and fluorine groups, gave rise to analogs displaying a TrxR inhibitory character positively correlated to their antiproliferative potencies. Lead analogs 2,2'-diOH-5,5'-diF-DPPen and 2-OH-5-F-DPPro yielded a half-maximal TrxR inhibitory concentration of 9.1 and 10.5 μM, respectively, after 1-h incubation with recombinant rat TrxR, with the C-terminal selenocysteine residue found to be targeted. Identification of Michael acceptor-centric pharmacophores among diversified compounds demonstrates that a systematic approach to discover and develop Michael acceptor-based TrxR inhibitors is feasible. A strong TrxR inhibitory character correlated to the antiproliferative potency is attributed to structural features that include an α,β-unsaturated carbonyl moiety centered in a DPPen or DPPro pharmacophore bearing hydroxyl and fluorine substitutions.