Search

Discovery of novel bioactive compounds is important not only for therapeutic purposes but also for understanding the mechanisms of biological processes. To screen bioactive compounds that affect nuclear morphology in marine organism extracts, we employed a microscopy-based assay using DNA staining of human cancer cells. A crude extract from a marine sponge Mycale aff. nullarosette, collected from the east coast of Japan, induced cellular binucleation. Fractionation of the extract led to the isolation of mycalolides A and B, and 38-hydroxymycalolide B as the active components. Mycalolides have been identified as marine toxins that induce depolymerization of the actin filament. Live cell imaging revealed that low concentrations of mycalolide A produce binucleated cells by inhibiting the completion of cytokinesis. At higher concentrations, however, mycalolide A causes immediate disruption of actin filaments and changes in cell morphology, yielding rounded cells. These results suggest that the completion of cytokinesis is a process requiring high actin polymerization activity. Furthermore, luciferase reporter assays with mycalolide A treatments support the view that the level of globular actin can affect transcription of a serum response gene.

BackgroundKnee osteoarthritis (OA) is a leading cause of disability among elderly individuals. Medical and surgical treatments are expensive and have side effects. The current study aimed to investigate the efficacy and safety of FlexC-II®, a type II collagen hydrolysate, and BRAND'S Essence of Chicken with FlexC-II® (BEC-FlexC-II®) on joint, muscle, and bone functions among elderly adults with OA.MethodsPatients (n = 160) with grade 1–3 knee OA based on the Kellgren–Lawrence classification system, joint pain for ≥3 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of >6 were considered eligible in this study. The participants were randomized into four groups (BEC-FlexC-II®, FlexC-II®, glucosamine hydrochloride [HCl], and placebo) and were instructed to perform resistance training for 24 weeks. The outcomes included WOMAC score, visual analogue scale (VAS) score, hand grip strength, fat-free mass (FFM), bone mass, and 36-Item Short-form Survey score. ResultsThe WOMAC scores of all groups improved after 24 weeks. However, the results did not significantly differ. Meanwhile, there was a remarkable difference in the VAS score between groups (P = 0.039). The FlexC-II® group had a greater reduction in pain than the placebo group (mean ± standard error: −1.3 ± 0.45, P = 0.021). In the FlexC-II® group, the VAS score significantly reduced by 0.9 ± 1.89 (P = 0.034) after 14 days. In the adjusted analyses, the BEC-FlexC-II® group had a significantly higher FFM than the glucosamine HCl (P = 0.02) and placebo (P = 0.017) groups and hand grip strength than the glucosamine HCl group (P = 0.002). Further, on the basis of a subgroup analysis, participants with poor training compliance in the BEC-FlexC-II® group had a significantly higher left hip bone mass than those in the placebo (P = 0.01) and glucosamine HCl (P = 0.049) groups.ConclusionsFlexC-II® relieves OA-associated pain within 14 days, and BEC-FlexC-II® increases muscle mass and strength after 24 weeks. Thus, BEC-Flex-CII® is a promising novel, holistic supplement that can improve mobility by promoting joint, muscle, and bone functions among elderly individuals. However, full-scale studies should be conducted in the future to validate these findings.Trial registrationThis clinical trial was retrospectively registered in ClinicalTrials.gov with the ID NCT04483024 on July 20, 2020. URL: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0008FK4&selectaction=Edit&uid=U0004BM2&ts=2&cx=-5y1oh4