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2024 Annual meeting of the international network on ectopic calcification (INTE...

Cancela, M. Leonor; Alouane, Ahmed; Bertelli, Pietro M.; Camacho, Antonio; Derudder, Robbe; Forlino, Antonella; Harris, Matthew P.; Jacinto, Marta

The 3rd Annual Meeting of the International Network on Ectopic Calcification (INTEC) was held in Faro, Portugal on 12–13 September 2024. This hybrid meeting brought together researchers and clinicians focused on the molecular, (patho)physiological, and clinical aspects of ectopic calcification in hereditary and acquired conditions, as well as in aging. The findings presented in this year’s meeting emphasised th...


FOXO1 represses PPARα-Mediated induction of FGF21 gene expression

De Sousa-Coelho, Ana Luísa; Gacias, Mar; O'Neill, Brian T.; Relat, Joana; Link, Wolfgang; Haro, Diego; Marrero, Pedro F.

Fibroblast growth factor 21 (FGF21) has emerged as a metabolic regulator that exerts potent anti-diabetic and lipid-lowering effects in animal models of obesity and type 2 diabetes, showing a protective role in fatty liver disease and hepatocellular carcinoma progression. Hepatic expression of FGF21 is regulated by PPARa and is induced by fasting. Ablation of FoxO1 in liver has been shown to increase FGF21 expr...


FOXO family isoforms

Santos, Bruno F; Grenho, Inês; Martel, Paulo; Ferreira, Bibiana; Link, Wolfgang

FOXO family of proteins are transcription factors involved in many physiological and pathological processes including cellular homeostasis, stem cell maintenance, cancer, metabolic, and cardiovascular diseases. Genetic evidence has been accumulating to suggest a prominent role of FOXOs in lifespan regulation in animal systems from hydra, C elegans, Drosophila, and mice. Together with the observation that FOXO3 ...


Retraction note: TRIB2 confers resistance to anti-cancer therapy by activating ...

Hill, Richard; Madureira, Patricia; Ferreira, Bibiana; Baptista, Ines; Machado, Susana; Colaҫo, Laura; dos Santos, Marta; Liu, Ningshu; Dopazo, Ana

The authors have retracted this article as it has come to their attention that several images were inappropriately processed and duplicated in multiple figures. In particular, the data were duplicated, and in some cases inverted, across several panels in Figures 2c, 2b, 3d and Supplementary Figure 5. Erroneous data were also included in Figure 2e, Supplementary Figure 1 and Supplementary Figure 8. We apologize ...


Synthesis, Characterization and Complex Evaluation of Antibacterial Activity an...

Slavchev, Ivaylo M.; Mitrev, Yavor; Shivachev, Boris; Valcheva, Violeta; Dogonadze, Marine; Solovieva, Natalia; Vyazovaya, Anna; Mokrousov, Igor

The synthesis of 20 arylidenecamphors and 15 pyrimidines with camphane skeleton is described in the current report. A modified method for preparation of sterically hindered 2-aminopyrimidines in two steps was demonstrated. The evaluation of their in vitro activity against Mycobacterium tuberculosis H37Rv showed different MIC values (up to 0.91 μM for ketone 39). Compound 35 demonstrated moderate (8.23 μM), but ...


Multiplexed cellular profiling identifies an organoselenium compound as an inhi...

Jimenez, Lucia; Mayoral‐Varo, Victor; Amenábar, Carlos; Ortega, Judit; Sequeira, João G. N.; Machuqueiro, Miguel; Mourato, Cristiana; Silvestri, Romano

Chromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and...


Screening health-promoting compounds for their capacity to induce the activity ...

Jimenez, Lucia; Silva, Andreia; Calissi, Giampaolo; Grenho, Inês; Monteiro, Ana Rita; Mayoral-Varo, Victor; Blanco-Aparicio, Carmen; Pastor, Joaquin

Several chemical compounds including natural products have been suggested as being effective against age-related diseases or as beneficial for a healthy life. On the other hand, forkhead box O (FOXO) proteins are emerging as key cellular components associated with extreme human longevity. FOXO proteins are mainly regulated by posttranslational modifications and as these modifications are reversible, activation ...


FOXO transcription factors as therapeutic targets in human diseases

Orea-Soufi, Alba; Paik, Jihye; Bragança, José; Donlon, Timothy A.; Willcox, Bradley J.; Link, Wolfgang

Forkhead box (FOX)O proteins are transcription factors (TFs) with four members in mammals designated FOXO1, FOXO3, FOXO4, and FOXO6. FOXO TFs play a pivotal role in the cellular adaptation to diverse stress conditions. FOXO proteins act as context-dependent tumor suppressors and their dysregulation has been implicated in several age-related diseases. FOXO3 has been established as a major gene for human longevit...


Decavanadate and metformin-decavanadate effects in human melanoma cells

de Sousa-Coelho, Ana Luísa; Aureliano, Manuel; Fraqueza, Gil; Serrão, Gisela; Gonçalves, João; Sánchez-Lombardo, Irma; Link, Wolfgang; Ferreira, Bibiana

Decavanadate is a polyoxometalate (POMs) that has shown extensive biological activities, including antidiabetic and anticancer activity. Importantly, vanadium-based compounds as well as antidiabetic biguanide drugs, such as metformin, have shown to exert therapeutic effects in melanoma. A combination of these agents, the metformin-decavanadate complex, was also recognized for its antidiabetic effects and recent...


mTORC2 Is the major second layer kinase negatively regulating FOXO3 activity

Jimenez, Lucia; Amenabar, Carlos; Mayoral-Varo, Victor; Mackenzie, Thomas A.; Ramos, Maria C.; Silva, Andreia; Calissi, Giampaolo; Grenho, Inês

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attain...


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