Mertensene, a halogenated monoterpene, induces G2/M cell cycle arrest and caspase dependent apoptosis of human colon adenocarcinoma HT29 cell line through the modulation of ERK-1/-2, AKT and NF-κB signaling

Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S.G. Gmelin) Santelices and Hommersand and we highlight its inhibitory effect on the viability of two human colorectal adenocarcinoma cell lines HT29 and LS174. Interestingly, exposure of HT29 cells to different concentrations of mertensene correlated with the activation of MAPK ERK-1/-2, Akt and NF-κB pathways. Moreover, mertensene-induced G2/M cell cycle arrest was associated with a decrease in the phosphorylated forms of the anti-tumor transcription factor p53, retinoblastoma protein (Rb), cdc2 and chkp2. Indeed, a reduction of the cellular level of cyclin-dependent kinases CDK2 and CDK4 was observed in mertensene-treated cells. We also demonstrated that mertensene triggers a caspase-dependent apoptosis in HT29 cancer cells characterized by the activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Besides, the level of death receptor-associated protein TRADD increased significantly in a concentration-dependent manner. Taken together, these results demonstrate the potential of mertensene as a drug candidate for the treatment of colon cancer. © 2017 by the authors. Licensee MDPI

Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures

Summary: Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods: Clinical perspective and updated literature search. Results: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions. © 2019, International Osteoporosis Foundation and National Osteoporosis Foundation

Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures

Summary Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods Clinical perspective and updated literature search. Results The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.</p

Correction to: Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures (Osteoporosis International, (2020), 31, 1, (1-12), 10.1007/s00198-019-05176-3)

The article ‘Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures’, written by J. A. Kanis, was originally published Online First without Open Access. After publication in volume [#], issue [#] and page [#-#], the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) (2019) and the article is forthwith distributed under the terms of a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/ by-nc/4.0/), which permits any non-commercial use, sharing, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source; provide a link to the Creative Commons licence and indicate if changes were made.The original article has been corrected

Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures

peer reviewe

Algorithm for the management of patients at low, high and very high risk osteoporotic fractures

SummaryGuidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures.IntroductionThe International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach.MethodsClinical perspective and updated literature search.ResultsThe following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis.ConclusionsA platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions