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The proliferation and differentiation of cultured epithelial cells may be modified by Rho-associated kinase (ROCK) inhibition and extracellular Ca2+ concentration. However, it was not known whether a combination would influence the behavior of cultured epithelial cells through changes in the phosphorylation of non-muscle myosin light chain II (MLC). Here we show that the combination of ROCK inhibition with Ca2+ elevation regulated the phosphorylation of MLC and improved both cell expansion and cell–cell adhesion during the culture of human nasal mucosal epithelial cell sheets. During explant culture, Ca2+ enhanced the adhesion of nasal mucosal tissue, while ROCK inhibition downregulated MLC phosphorylation and promoted cell proliferation. During cell sheet culture, an elevation of extracellular Ca2+ promoted MLC phosphorylation and formation of cell–cell junctions, allowing the harvesting of cell sheets without collapse. Moreover, an in vitro grafting assay revealed that ROCK inhibition increased the expansion of cell sheets three-fold (an effect maintained when Ca2+ was also elevated), implying better wound healing potential. We suggest that combining ROCK inhibition with elevation of Ca2+ could facilitate the fabrication of many types of cell graft. [ABSTRACT FROM AUTHOR]

Introduction: There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation of the type of foods/beverages people consumed and the risk reduction of contracting COVID-19 and the recovery from COVID-19., Methods: We developed an online survey that asked the participants whether they contracted COVID-19, their symptoms, time to recover, and their frequency of eating various types of foods/beverages. The survey was developed in 10 different languages., Results: The participants who did not contract COVID-19 consumed vegetables, herbs/spices, and fermented foods/beverages significantly more than the participants who contracted COVID-19. Among the six countries (India/Iran/Italy/Japan/Russia/Spain) with over 100 participants and high correspondence between the location of the participants and the language of the survey, in India and Japan the people who contracted COVID-19 showed significantly shorter recovery time, and greater daily intake of vegetables, herbs/spices, and fermented foods/beverages was associated with faster recovery., Conclusions: Our results suggest that phytochemical compounds included in the vegetables may have contributed in not only preventing contraction of COVID-19, but also accelerating their recovery., (Copyright © 2024 Koyama, Joseph, Shields, Heinbockel, Adhikari, Kaur, Kumar, Alizadeh, Bhutani, Calcinoni, Mucignat-Caretta, Chen, Cooper, Das, Rohlfs Domínguez, Guàrdia, Klyuchnikova, Laktionova, Mori, Namjoo, Nguyen, Özdener, Parsa, Özdener Poyraz, Strub, Taghizadeh-Hesary, Ueha and Voznessenskaya.)

Estrogen receptor (ER) is a hormone-inducible transcription factor as a member of the nuclear receptor gene superfamily. Unliganded ER is transcriptionally silent and capable of DNA binding; however, it is unable to suppress the basal activity of the target gene promoters, unlike non-steroid hormone receptors that associate with corepressors in the absence of their cognate ligands. To study the molecular basis of how unliganded human ERalpha is maintained silent in gene regulation upon the target gene promoters, we biochemically searched interactants for hERalpha, and identified heat shock protein 70 (Hsc70). Hsc70 appeared to associate with the N-terminal hormone binding E domain, that also turned out a transcriptionally repressive domain. Competitive association of Hsc70 with a best known coactivator p300 was observed. Thus, these findings suggest that Hsc70 associates with unliganded hERalpha, and thereby deters hERalpha from recruiting transcriptional coregulators, presumably as a component of chaperone complexes.