Author: Abedrabbo, Maha ; Caldas, Carlos ; Bernshtein, Karin Shira ; Rueda, Oscar M. ; Giri, Suvendu ; Lindzen, Moshit ; Chatterjee, Rishita ; Sekar, Arunachalam ; Nair, Nishanth Ulhas ; Blandino, Giovanni ; Zhu, Rong ; Sanghvi, Neel ; Shiloh, Yosef ; Lev, Sima ; Dahlhoff, Maik ; Alon, Ronen ; Gupta, Nitin ; Drago-Garcia, Diana ; Pikarsky, Eli ; Wiemann, Stefan ; Roncato, Francesco ; Mayalagu, Agalyan ; Tarade, Nooraldeen ; Keidar, Tal ; Mohan-Raju, Harsha-Raj ; Wagner, Bettina ; Genna, Alessandro ; Prywes, Ron ; Schwarzmüller, Luisa ; Aharoni, Noa ; Belugali Nataraj, Nishanth ; Rios, Mary Luz Uribe ; Seger, Rony ; Nof, Yam ; Yarden, Yosef ; Eyal-Lubling, Yaniv ; Ruppin, Eytan ; Simoni-Nieves, Arturo ; Barkan, Dalit ; Karatekin, Feride ; Donzelli, Sara ; Bhandari, Tithi

Cellular plasticity mediates tissue development as well as cancer growth and progression. In breast cancer, a shift to a more epithelial phenotype (epithelialization) underlies a state of reversible cell growth arrest called tumor dormancy, which enables drug resistance, tumor recurrence, and metastasis. Here, we explored the mechanisms driving epithelialization and dormancy in aggressive mesenchymal-like breast cancer cells in three-dimensional cultures. Overexpressing either of the epithelial lineage-associated transcription factors OVOL1 or OVOL2 suppressed cell proliferation and migration and promoted transition to an epithelial morphology. The expression of OVOL1 (and of OVOL2 to a lesser extent) was regulated by steroid hormones and growth factors and was more abundant in tumors than in normal mammary cells. An uncharacterized and indirect target of OVOL1/2, C1ORF116 , exhibited genetic and epigenetic aberrations in breast tumors, and its expression correlated with poor prognosis in patients. We further found that C1ORF116 was an autophagy receptor that directed the degradation of antioxidant proteins, including thioredoxin. Through C1ORF116 and unidentified mediators, OVOL1 expression dysregulated both redox homeostasis (in association with increased ROS, decreased glutathione, and redistribution of the transcription factor NRF2) and DNA damage and repair (in association with increased DNA oxidation and double-strand breaks and an altered interplay among the kinases p38-MAPK, ATM, and others). Because these effects, as they accumulate in cells, can promote metastasis and dormancy escape, the findings suggest that OVOLs not only promote dormancy entry and maintenance in breast cancer but also may ultimately drive dormancy exit and tumor recurrence.

21 Apr 2025·ACS Agricultural Science & Technology

Phycobiostimulants: Next-Generation Sustainable Agricultural Inputs

Author: Shukla, Pushp Sheel ; Bourgougnon, Nathalie ; Critchley, Alan T. ; Daridon, Bruno ; Hurtado, Anicia ; Ronga, Domenico ; Burlot, Anne-Sophie ; Michalak, Izabela

Plant biostimulants are a novel class of naturally derived agricultural inputs.The grouping of categories within the regulatory term "biostimulant" contains disparate inputs, such as humates, amino acids, bacteria, and algal extracts (i.e., many extraction processes applied to a relatively small group of selected seaweeds/microalgae).All seem to have the ability to improve the health and abiotic stress resistance of the treated plants.Even extracts of seaweeds (phycobiostimulants) are considerably different from one another (they are not all the same yet commonly referred to as seaweed extract, even in peer-reviewed publications), and current com. offerings are available from a select group of green, red, and brown seaweeds.Com. formulations combine different seaweed extracts and increasingly leverage synergies by blending biostimulants with other agricultural inputs and agrochems.Extensive research highlights that various algal-based extracts can effectively support both abiotic and biotic stress resistance when applied to both treated terrestrial plants and other cultivated algae.This article explores the scientific nuances of phycobiostimulants, challenging traditional regulatory classifications and emphasizing their essential role in sustainable agronomy, growing phyconomy, and global food security.

01 Apr 2025·APIK Journal of Internal Medicine

The Good Clinical Practice: The Road Ahead in 2025

Author: Jonnalagadda, Venu Gopal

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